Search

Your search keyword '"Venditti, Rossella"' showing total 138 results
Start Over Author "Venditti, Rossella"
138 results on '"Venditti, Rossella"'

1. Two FAM134B isoforms differentially regulate ER dynamics during myogenesis

Author

Buonomo, Viviana, Lohachova, Kateryna, Reggio, Alessio, Cano-Franco, Sara, Cillo, Michele, Santorelli, Lucia, Venditti, Rossella, Polishchuk, Elena, Peluso, Ivana, Brunello, Lorene, Cirillo, Carmine, Petrosino, Sara, Silva, Malan, De Cegli, Rossella, Di Bartolomeo, Sabrina, Gargioli, Cesare, Swuec, Paolo, Cortese, Mirko, Stolz, Alexandra, Bhaskara, Ramachandra M, and Grumati, Paolo

Published
2025
Full Text
View/download PDF

2. Membrane Trafficking to the Extracellular Matrix and Skeletal Dysplasia

Author

Guarino, Andrea Maria, Venditti, Rossella, Wilson, Cathal, Karamanos, Nikos K., Series Editor, Kletsas, Dimitris, Editorial Board Member, Oh, Eok-Soo, Editorial Board Member, Passi, Alberto, Editorial Board Member, Pihlajaniemi, Taina, Editorial Board Member, Ricard-Blum, Sylvie, Editorial Board Member, Sagi, Irit, Editorial Board Member, Savani, Rashmin, Editorial Board Member, Watanabe, Hideto, Editorial Board Member, Rossi, Antonio, editor, and Zaucke, Frank, editor

Published
2024
Full Text
View/download PDF

3. De novo missense variants in phosphatidylinositol kinase PIP5KIγ underlie a neurodevelopmental syndrome associated with altered phosphoinositide signaling

Author

Acosta, Maria T., Adam, Margaret, Adams, David R., Alvarez, Raquel L., Alvey, Justin, Amendola, Laura, Andrews, Ashley, Ashley, Euan A., Bacino, Carlos A., Bademci, Guney, Balasubramanyam, Ashok, Baldridge, Dustin, Bale, Jim, Bamshad, Michael, Barbouth, Deborah, Bayrak-Toydemir, Pinar, Beck, Anita, Beggs, Alan H., Behrens, Edward, Bejerano, Gill, Bellen, Hugo J., Bennett, Jimmy, Berg-Rood, Beverly, Bernstein, Jonathan A., Berry, Gerard T., Bican, Anna, Bivona, Stephanie, Blue, Elizabeth, Bohnsack, John, Bonner, Devon, Botto, Lorenzo, Boyd, Brenna, Briere, Lauren C., Brown, Gabrielle, Burke, Elizabeth A., Burrage, Lindsay C., Butte, Manish J., Byers, Peter, Byrd, William E., Carey, John, Carrasquillo, Olveen, Cassini, Thomas, Chang, Ta Chen Peter, Chanprasert, Sirisak, Chao, Hsiao-Tuan, Clark, Gary D., Coakley, Terra R., Cobban, Laurel A., Cogan, Joy D., Coggins, Matthew, Cole, F. Sessions, Colley, Heather A., Cooper, Cynthia M., Cope, Heidi, Corona, Rosario, Craigen, William J., Crouse, Andrew B., Cunningham, Michael, D’Souza, Precilla, Dai, Hongzheng, Dasari, Surendra, Davis, Joie, Dayal, Jyoti G., Dell'Angelica, Esteban C., Dipple, Katrina, Doherty, Daniel, Dorrani, Naghmeh, Doss, Argenia L., Douine, Emilie D., Earl, Dawn, Eckstein, David J., Emrick, Lisa T., Eng, Christine M., Falk, Marni, Fieg, Elizabeth L., Fisher, Paul G., Fogel, Brent L., Forghani, Irman, Gahl, William A., Glass, Ian, Gochuico, Bernadette, Goddard, Page C., Godfrey, Rena A., Golden-Grant, Katie, Grajewski, Alana, Hadley, Don, Hahn, Sihoun, Halley, Meghan C., Hamid, Rizwan, Hassey, Kelly, Hayes, Nichole, High, Frances, Hing, Anne, Hisama, Fuki M., Holm, Ingrid A., Hom, Jason, Horike-Pyne, Martha, Huang, Alden, Hutchison, Sarah, Introne, Wendy, Isasi, Rosario, Izumi, Kosuke, Jamal, Fariha, Jarvik, Gail P., Jarvik, Jeffrey, Jayadev, Suman, Jean-Marie, Orpa, Jobanputra, Vaidehi, Karaviti, Lefkothea, Ketkar, Shamika, Kiley, Dana, Kilich, Gonench, Kobren, Shilpa N., Kohane, Isaac S., Kohler, Jennefer N., Korrick, Susan, Kozuira, Mary, Krakow, Deborah, Krasnewich, Donna M., Kravets, Elijah, Lalani, Seema R., Lam, Byron, Lam, Christina, Lanpher, Brendan C., Lanza, Ian R., LeBlanc, Kimberly, Lee, Brendan H., Levitt, Roy, Lewis, Richard A., Liu, Pengfei, Liu, Xue Zhong, Longo, Nicola, Loo, Sandra K., Loscalzo, Joseph, Maas, Richard L., Macnamara, Ellen F., MacRae, Calum A., Maduro, Valerie V., Maghiro, AudreyStephannie, Mahoney, Rachel, Malicdan, May Christine V., Mamounas, Laura A., Manolio, Teri A., Mao, Rong, Maravilla, Kenneth, Marom, Ronit, Marth, Gabor, Martin, Beth A., Martin, Martin G., Martínez-Agosto, Julian A., Marwaha, Shruti, McCauley, Jacob, McConkie-Rosell, Allyn, McCray, Alexa T., McGee, Elisabeth, Mefford, Heather, Merritt, J. Lawrence, Might, Matthew, Mirzaa, Ghayda, Morava, Eva, Moretti, Paolo, Mulvihill, John, Nakano-Okuno, Mariko, Nelson, Stanley F., Newman, John H., Nicholas, Sarah K., Nickerson, Deborah, Nieves-Rodriguez, Shirley, Novacic, Donna, Oglesbee, Devin, Orengo, James P., Pace, Laura, Pak, Stephen, Pallais, J. Carl, Palmer, Christina G.S., Papp, Jeanette C., Parker, Neil H., Phillips III, John A., Posey, Jennifer E., Potocki, Lorraine, Pusey Swerdzewski, Barbara N., Quinlan, Aaron, Rao, Deepak A., Raper, Anna, Raskind, Wendy, Renteria, Genecee, Reuter, Chloe M., Rives, Lynette, Robertson, Amy K., Rodan, Lance H., Rosenfeld, Jill A., Rosenwasser, Natalie, Rossignol, Francis, Ruzhnikov, Maura, Sacco, Ralph, Sampson, Jacinda B., Saporta, Mario, Schaechter, Judy, Schedl, Timothy, Schoch, Kelly, Scott, Daryl A., Scott, C. Ron, Shashi, Vandana, Shin, Jimann, Silverman, Edwin K., Sinsheimer, Janet S., Sisco, Kathy, Smith, Edward C., Smith, Kevin S., Solnica-Krezel, Lilianna, Solomon, Ben, Spillmann, Rebecca C., Stoler, Joan M., Sullivan, Kathleen, Sullivan, Jennifer A., Sun, Angela, Sutton, Shirley, Sweetser, David A., Sybert, Virginia, Tabor, Holly K., Tan, Queenie K.-G., Tan, Amelia L.M., Tekin, Mustafa, Telischi, Fred, Thorson, Willa, Tifft, Cynthia J., Toro, Camilo, Tran, Alyssa A., Ungar, Rachel A., Urv, Tiina K., Vanderver, Adeline, Velinder, Matt, Viskochil, Dave, Vogel, Tiphanie P., Wahl, Colleen E., Walker, Melissa, Wallace, Stephanie, Walley, Nicole M., Wambach, Jennifer, Wan, Jijun, Wang, Lee-kai, Wangler, Michael F., Ward, Patricia A., Wegner, Daniel, Weisz Hubshman, Monika, Wener, Mark, Wenger, Tara, Westerfield, Monte, Wheeler, Matthew T., Whitlock, Jordan, Wolfe, Lynne A., Worley, Kim, Xiao, Changrui, Yamamoto, Shinya, Yang, John, Zhang, Zhe, Zuchner, Stephan, Nigro, Vincenzo, Torella, Annalaura, Morleo, Manuela, Spampanato, Carmine, Pinelli, Michele, Banfi, Sandro, Varavallo, Alessandra, Selicorni, Angelo, Mariani, Milena, Massimello, Marta, Daolio, Cecilia, Capra, Valeria, Accogli, Andrea, Scala, Marcello, Leuzzi, Vincenzo, Nardecchia, Francesca, Galosi, Serena, Mastrangelo, Mario, Milani, Donatella, Vitiello, Giuseppina, Piluso, Giulio, Romano, Corrado, Failla, Pinella, Greco, Donatella, Pantaleoni, Chiara, Ciaccio, Claudia, D’Arrigo, Stefano, Brunetti Pierri, Nicola, Parenti, Giancarlo, Coppola, Antonietta, Mattina, Teresa, Zollino, Marcella, Amenta, Simona, Tummolo, Albina, Santoro, Claudia, Grandone, Anna, De Brasi, Daniele, Varone, Antonio, Garavelli, Livia, Marini, Carla, Bigoni, Stefania, Piscopo, Carmelo, Trabacca, Antonio, De Rinaldis, Marta, Peron, Angela, Venditti, Rossella, Theodorou, Evangelos, Rosello, Marion, Tirozzi, Alfonsina, Tammaro, Roberta, Al-Badri, Nour, High, Frances A., Shi, Jiahai, Putti, Elena, Ferrante, Luigi, Cetrangolo, Viviana, Walker, Melissa A., Tenconi, Romano, Iascone, Maria, Mei, Davide, Guerrini, Renzo, van der Smagt, Jasper, Kroes, Hester Y., van Gassen, Koen L.I., Bilal, Muhammad, Umair, Muhammad, Pingault, Veronica, Attie-Bitach, Tania, Amiel, Jeannine, Ejaz, Resham, Rodan, Lance, Agrawal, Pankaj B., Del Bene, Filippo, and Franco, Brunella

Published
2023
Full Text
View/download PDF

5. The role of NSP6 in the biogenesis of the SARS-CoV-2 replication organelle

Author

Ricciardi, Simona, Guarino, Andrea Maria, Giaquinto, Laura, Polishchuk, Elena V., Santoro, Michele, Di Tullio, Giuseppe, Wilson, Cathal, Panariello, Francesco, Soares, Vinicius C., Dias, Suelen S. G., Santos, Julia C., Souza, Thiago M. L., Fusco, Giovanna, Viscardi, Maurizio, Brandi, Sergio, Bozza, Patrícia T., Polishchuk, Roman S., Venditti, Rossella, and De Matteis, Maria Antonietta

Published
2022
Full Text
View/download PDF

7. COPB2 loss of function causes a coatopathy with osteoporosis and developmental delay

Author

Marom, Ronit, Burrage, Lindsay C., Venditti, Rossella, Clément, Aurélie, Blanco-Sánchez, Bernardo, Jain, Mahim, Scott, Daryl A., Rosenfeld, Jill A., Sutton, V. Reid, Shinawi, Marwan, Mirzaa, Ghayda, DeVile, Catherine, Roberts, Rowenna, Calder, Alistair D., Allgrove, Jeremy, Grafe, Ingo, Lanza, Denise G., Li, Xiaohui, Joeng, Kyu Sang, Lee, Yi-Chien, Song, I-Wen, Sliepka, Joseph M., Batkovskyte, Dominyka, Washington, Megan, Dawson, Brian C., Jin, Zixue, Jiang, Ming-Ming, Chen, Shan, Chen, Yuqing, Tran, Alyssa A., Emrick, Lisa T., Murdock, David R., Hanchard, Neil A., Zapata, Gladys E., Mehta, Nitesh R., Weis, Mary Ann, Scott, Abbey A., Tremp, Brenna A., Phillips, Jennifer B., Wegner, Jeremy, Taylor-Miller, Tashunka, Gibbs, Richard A., Muzny, Donna M., Jhangiani, Shalini N., Hicks, John, Stottmann, Rolf W., Dickinson, Mary E., Seavitt, John R., Heaney, Jason D., Eyre, David R., Westerfield, Monte, De Matteis, Maria Antonietta, and Lee, Brendan

Published
2021
Full Text
View/download PDF

11. Role of sedlin, a TRAPP complex subunit, in membrane trafficking and in the pathogenesis of Spondyleopyphiseal Dysplasia Tarda

Author

Venditti, Rossella

Subjects
616.7
Abstract

Genetic defects occurring in the sedlin gene, a conserved component of TRAPP complex, cause Spondyloepiphyseal Dysplasia Tarda (SEDT), a rare progressive condition characterised by impaired chondrogenesis resulting in short stature, flattening of the vertebrae, and premature osteoarthritis. The role of sedlin in the pathogenesis of SEDT disease so far is still unknown. Prompted by the consideration that sedlin is ubiquitously expressed but that sedlin mutations cause cartilaginous-restricted dysfunctions, I hypothesized that sedlin might exert a role in membrane trafficking generally but in particular in the transport of chondrocyte- specific cargoes, such as type II procollagen (PCII). This hypothesis was reinforced by the fact that mutations in PCII give rise to autosomal dominant forms of spondyloepiphiseal dysplasia. I tested this hypothesis by analyzing the involvement of sedlin in the transport of different classes of secretory cargoes and found that sedlin is selectively required for PCII to exit the ER, while it is not essential for ER exit of small soluble and membrane-associated cargoes. I have also identified the molecular mechanism underlying this role of sedlin in its ability to bind the GTPase Sarl and to control the membrane-cytosol cycle of Sarl itself and of the COPIl coat complex at the level of the ER exit sites. Sedlin depletion and/or mutation in SEDT patients slows down the Sar1 cycle and prolongs the membrane association of Sar1-GTP at the ER exit sites, thus inducing constriction and premature fission of nascent carriers which fail to incorporate the large PC protofibrils but are still competent for smaller secretory cargoes. All together these findings provide new insights not only into understanding the role of sedlin but also shed new light on the molecular mechanisms underlying the onset of the SEDT disease.

Published
2011
Full Text
View/download PDF

12. De novo missense variants in phosphatidylinositol kinase PIP5KIγ underlie a neurodevelopmental syndrome associated with altered phosphoinositide signaling

Author

Morleo, Manuela, primary, Venditti, Rossella, additional, Theodorou, Evangelos, additional, Briere, Lauren C., additional, Rosello, Marion, additional, Tirozzi, Alfonsina, additional, Tammaro, Roberta, additional, Al-Badri, Nour, additional, High, Frances A., additional, Shi, Jiahai, additional, Putti, Elena, additional, Ferrante, Luigi, additional, Cetrangolo, Viviana, additional, Torella, Annalaura, additional, Walker, Melissa A., additional, Tenconi, Romano, additional, Iascone, Maria, additional, Mei, Davide, additional, Guerrini, Renzo, additional, van der Smagt, Jasper, additional, Kroes, Hester Y., additional, van Gassen, Koen L.I., additional, Bilal, Muhammad, additional, Umair, Muhammad, additional, Pingault, Veronica, additional, Attie-Bitach, Tania, additional, Amiel, Jeannine, additional, Ejaz, Resham, additional, Rodan, Lance, additional, Zollino, Marcella, additional, Agrawal, Pankaj B., additional, Del Bene, Filippo, additional, Nigro, Vincenzo, additional, Sweetser, David A., additional, Franco, Brunella, additional, Acosta, Maria T., additional, Adam, Margaret, additional, Adams, David R., additional, Alvarez, Raquel L., additional, Alvey, Justin, additional, Amendola, Laura, additional, Andrews, Ashley, additional, Ashley, Euan A., additional, Bacino, Carlos A., additional, Bademci, Guney, additional, Balasubramanyam, Ashok, additional, Baldridge, Dustin, additional, Bale, Jim, additional, Bamshad, Michael, additional, Barbouth, Deborah, additional, Bayrak-Toydemir, Pinar, additional, Beck, Anita, additional, Beggs, Alan H., additional, Behrens, Edward, additional, Bejerano, Gill, additional, Bellen, Hugo J., additional, Bennett, Jimmy, additional, Berg-Rood, Beverly, additional, Bernstein, Jonathan A., additional, Berry, Gerard T., additional, Bican, Anna, additional, Bivona, Stephanie, additional, Blue, Elizabeth, additional, Bohnsack, John, additional, Bonner, Devon, additional, Botto, Lorenzo, additional, Boyd, Brenna, additional, Brown, Gabrielle, additional, Burke, Elizabeth A., additional, Burrage, Lindsay C., additional, Butte, Manish J., additional, Byers, Peter, additional, Byrd, William E., additional, Carey, John, additional, Carrasquillo, Olveen, additional, Cassini, Thomas, additional, Chang, Ta Chen Peter, additional, Chanprasert, Sirisak, additional, Chao, Hsiao-Tuan, additional, Clark, Gary D., additional, Coakley, Terra R., additional, Cobban, Laurel A., additional, Cogan, Joy D., additional, Coggins, Matthew, additional, Cole, F. Sessions, additional, Colley, Heather A., additional, Cooper, Cynthia M., additional, Cope, Heidi, additional, Corona, Rosario, additional, Craigen, William J., additional, Crouse, Andrew B., additional, Cunningham, Michael, additional, D’Souza, Precilla, additional, Dai, Hongzheng, additional, Dasari, Surendra, additional, Davis, Joie, additional, Dayal, Jyoti G., additional, Dell'Angelica, Esteban C., additional, Dipple, Katrina, additional, Doherty, Daniel, additional, Dorrani, Naghmeh, additional, Doss, Argenia L., additional, Douine, Emilie D., additional, Earl, Dawn, additional, Eckstein, David J., additional, Emrick, Lisa T., additional, Eng, Christine M., additional, Falk, Marni, additional, Fieg, Elizabeth L., additional, Fisher, Paul G., additional, Fogel, Brent L., additional, Forghani, Irman, additional, Gahl, William A., additional, Glass, Ian, additional, Gochuico, Bernadette, additional, Goddard, Page C., additional, Godfrey, Rena A., additional, Golden-Grant, Katie, additional, Grajewski, Alana, additional, Hadley, Don, additional, Hahn, Sihoun, additional, Halley, Meghan C., additional, Hamid, Rizwan, additional, Hassey, Kelly, additional, Hayes, Nichole, additional, High, Frances, additional, Hing, Anne, additional, Hisama, Fuki M., additional, Holm, Ingrid A., additional, Hom, Jason, additional, Horike-Pyne, Martha, additional, Huang, Alden, additional, Hutchison, Sarah, additional, Introne, Wendy, additional, Isasi, Rosario, additional, Izumi, Kosuke, additional, Jamal, Fariha, additional, Jarvik, Gail P., additional, Jarvik, Jeffrey, additional, Jayadev, Suman, additional, Jean-Marie, Orpa, additional, Jobanputra, Vaidehi, additional, Karaviti, Lefkothea, additional, Ketkar, Shamika, additional, Kiley, Dana, additional, Kilich, Gonench, additional, Kobren, Shilpa N., additional, Kohane, Isaac S., additional, Kohler, Jennefer N., additional, Korrick, Susan, additional, Kozuira, Mary, additional, Krakow, Deborah, additional, Krasnewich, Donna M., additional, Kravets, Elijah, additional, Lalani, Seema R., additional, Lam, Byron, additional, Lam, Christina, additional, Lanpher, Brendan C., additional, Lanza, Ian R., additional, LeBlanc, Kimberly, additional, Lee, Brendan H., additional, Levitt, Roy, additional, Lewis, Richard A., additional, Liu, Pengfei, additional, Liu, Xue Zhong, additional, Longo, Nicola, additional, Loo, Sandra K., additional, Loscalzo, Joseph, additional, Maas, Richard L., additional, Macnamara, Ellen F., additional, MacRae, Calum A., additional, Maduro, Valerie V., additional, Maghiro, AudreyStephannie, additional, Mahoney, Rachel, additional, Malicdan, May Christine V., additional, Mamounas, Laura A., additional, Manolio, Teri A., additional, Mao, Rong, additional, Maravilla, Kenneth, additional, Marom, Ronit, additional, Marth, Gabor, additional, Martin, Beth A., additional, Martin, Martin G., additional, Martínez-Agosto, Julian A., additional, Marwaha, Shruti, additional, McCauley, Jacob, additional, McConkie-Rosell, Allyn, additional, McCray, Alexa T., additional, McGee, Elisabeth, additional, Mefford, Heather, additional, Merritt, J. Lawrence, additional, Might, Matthew, additional, Mirzaa, Ghayda, additional, Morava, Eva, additional, Moretti, Paolo, additional, Mulvihill, John, additional, Nakano-Okuno, Mariko, additional, Nelson, Stanley F., additional, Newman, John H., additional, Nicholas, Sarah K., additional, Nickerson, Deborah, additional, Nieves-Rodriguez, Shirley, additional, Novacic, Donna, additional, Oglesbee, Devin, additional, Orengo, James P., additional, Pace, Laura, additional, Pak, Stephen, additional, Pallais, J. Carl, additional, Palmer, Christina G.S., additional, Papp, Jeanette C., additional, Parker, Neil H., additional, Phillips III, John A., additional, Posey, Jennifer E., additional, Potocki, Lorraine, additional, Pusey Swerdzewski, Barbara N., additional, Quinlan, Aaron, additional, Rao, Deepak A., additional, Raper, Anna, additional, Raskind, Wendy, additional, Renteria, Genecee, additional, Reuter, Chloe M., additional, Rives, Lynette, additional, Robertson, Amy K., additional, Rodan, Lance H., additional, Rosenfeld, Jill A., additional, Rosenwasser, Natalie, additional, Rossignol, Francis, additional, Ruzhnikov, Maura, additional, Sacco, Ralph, additional, Sampson, Jacinda B., additional, Saporta, Mario, additional, Schaechter, Judy, additional, Schedl, Timothy, additional, Schoch, Kelly, additional, Scott, Daryl A., additional, Scott, C. Ron, additional, Shashi, Vandana, additional, Shin, Jimann, additional, Silverman, Edwin K., additional, Sinsheimer, Janet S., additional, Sisco, Kathy, additional, Smith, Edward C., additional, Smith, Kevin S., additional, Solnica-Krezel, Lilianna, additional, Solomon, Ben, additional, Spillmann, Rebecca C., additional, Stoler, Joan M., additional, Sullivan, Kathleen, additional, Sullivan, Jennifer A., additional, Sun, Angela, additional, Sutton, Shirley, additional, Sybert, Virginia, additional, Tabor, Holly K., additional, Tan, Queenie K.-G., additional, Tan, Amelia L.M., additional, Tekin, Mustafa, additional, Telischi, Fred, additional, Thorson, Willa, additional, Tifft, Cynthia J., additional, Toro, Camilo, additional, Tran, Alyssa A., additional, Ungar, Rachel A., additional, Urv, Tiina K., additional, Vanderver, Adeline, additional, Velinder, Matt, additional, Viskochil, Dave, additional, Vogel, Tiphanie P., additional, Wahl, Colleen E., additional, Walker, Melissa, additional, Wallace, Stephanie, additional, Walley, Nicole M., additional, Wambach, Jennifer, additional, Wan, Jijun, additional, Wang, Lee-kai, additional, Wangler, Michael F., additional, Ward, Patricia A., additional, Wegner, Daniel, additional, Weisz Hubshman, Monika, additional, Wener, Mark, additional, Wenger, Tara, additional, Westerfield, Monte, additional, Wheeler, Matthew T., additional, Whitlock, Jordan, additional, Wolfe, Lynne A., additional, Worley, Kim, additional, Xiao, Changrui, additional, Yamamoto, Shinya, additional, Yang, John, additional, Zhang, Zhe, additional, Zuchner, Stephan, additional, Morleo, Manuela, additional, Spampanato, Carmine, additional, Pinelli, Michele, additional, Banfi, Sandro, additional, Varavallo, Alessandra, additional, Selicorni, Angelo, additional, Mariani, Milena, additional, Massimello, Marta, additional, Daolio, Cecilia, additional, Capra, Valeria, additional, Accogli, Andrea, additional, Scala, Marcello, additional, Leuzzi, Vincenzo, additional, Nardecchia, Francesca, additional, Galosi, Serena, additional, Mastrangelo, Mario, additional, Milani, Donatella, additional, Vitiello, Giuseppina, additional, Piluso, Giulio, additional, Romano, Corrado, additional, Failla, Pinella, additional, Greco, Donatella, additional, Pantaleoni, Chiara, additional, Ciaccio, Claudia, additional, D’Arrigo, Stefano, additional, Brunetti Pierri, Nicola, additional, Parenti, Giancarlo, additional, Coppola, Antonietta, additional, Mattina, Teresa, additional, Amenta, Simona, additional, Tummolo, Albina, additional, Santoro, Claudia, additional, Grandone, Anna, additional, De Brasi, Daniele, additional, Varone, Antonio, additional, Garavelli, Livia, additional, Marini, Carla, additional, Bigoni, Stefania, additional, Piscopo, Carmelo, additional, Trabacca, Antonio, additional, De Rinaldis, Marta, additional, and Peron, Angela, additional

Published
2023
Full Text
View/download PDF

13. De novo missense variants in phosphatidylinositol kinase PIP5KIγ underlie a neurodevelopmental syndrome associated with altered phosphoinositide signaling

Author

Morleo, Manuela, Venditti, Rossella, Theodorou, Evangelos, Briere, Lauren C, Rosello, Marion, Tirozzi, Alfonsina, Tammaro, Roberta, Al-Badri, Nour, High, Frances A, Shi, Jiahai, Putti, Elena, Ferrante, Luigi, Cetrangolo, Viviana, Torella, Annalaura, Walker, Melissa A, Tenconi, Romano, Iascone, Maria, Mei, Davide, Guerrini, Renzo, van der Smagt, Jasper, Kroes, Hester Y, van Gassen, Koen L I, Bilal, Muhammad, Umair, Muhammad, Pingault, Veronica, Attie-Bitach, Tania, Amiel, Jeannine, Ejaz, Resham, Rodan, Lance, Zollino, Marcella, Agrawal, Pankaj B, Del Bene, Filippo, Nigro, Vincenzo, Sweetser, David A, Franco, Brunella, Morleo, Manuela, Venditti, Rossella, Theodorou, Evangelo, Briere, Lauren C, Rosello, Marion, Tirozzi, Alfonsina, Tammaro, Roberta, Al-Badri, Nour, High, Frances A, Shi, Jiahai, Putti, Elena, Ferrante, Luigi, Cetrangolo, Viviana, Torella, Annalaura, Walker, Melissa A, Tenconi, Romano, Iascone, Maria, Mei, Davide, Guerrini, Renzo, van der Smagt, Jasper, Kroes, Hester Y, van Gassen, Koen L I, Bilal, Muhammad, Umair, Muhammad, Pingault, Veronica, Attie-Bitach, Tania, Amiel, Jeannine, Ejaz, Resham, Rodan, Lance, Zollino, Marcella, Agrawal, Pankaj B, Del Bene, Filippo, Nigro, Vincenzo, Sweetser, David A, and Franco, Brunella

Subjects
PIP5K1C, developmental delay, intellectual disability, phosphatidylinositol 4,5 bisphosphate (PI(4,5)P(2)), de novo gain-of-function variant, zebrafish, endosome, phosphoinositide
Abstract

Phosphoinositides (PIs) are membrane phospholipids produced through the local activity of PI kinases and phosphatases that selectively add or remove phosphate groups from the inositol head group. PIs control membrane composition and play key roles in many cellular processes including actin dynamics, endosomal trafficking, autophagy, and nuclear functions. Mutations in phosphatidylinositol 4,5 bisphosphate [PI(4,5)P2] phosphatases cause a broad spectrum of neurodevelopmental disorders such as Lowe and Joubert syndromes and congenital muscular dystrophy with cataracts and intellectual disability, which are thus associated with increased levels of PI(4,5)P2. Here, we describe a neurodevelopmental disorder associated with an increase in the production of PI(4,5)P2 and with PI-signaling dysfunction. We identified three de novo heterozygous missense variants in PIP5K1C, which encodes an isoform of the phosphatidylinositol 4-phosphate 5-kinase (PIP5KIγ), in nine unrelated children exhibiting intellectual disability, developmental delay, acquired microcephaly, seizures, visual abnormalities, and dysmorphic features. We provide evidence that the PIP5K1C variants result in an increase of the endosomal PI(4,5)P2 pool, giving rise to ectopic recruitment of filamentous actin at early endosomes (EEs) that in turn causes dysfunction in EE trafficking. In addition, we generated an invivo zebrafish model that recapitulates the disorder we describe with developmental defects affecting the forebrain, including the eyes, as well as craniofacial abnormalities, further demonstrating the pathogenic effect of the PIP5K1C variants.

Published
2023

17. FGF signalling regulates bone growth through autophagy

Author

Cinque, Laura, Forrester, Alison, Bartolomeo, Rosa, Svelto, Maria, Venditti, Rossella, Montefusco, Sandro, Polishchuk, Elena, Nusco, Edoardo, Rossi, Antonio, Medina, Diego L., Polishchuk, Roman, De Matteis, Maria Antonietta, and Settembre, Carmine

Subjects
Autophagy (Cytology) -- Physiological aspects, Bones -- Growth, Fibroblast growth factors -- Physiological aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Skeletal growth relies on both biosynthetic and catabolic processes (1,2). While the role of the former is clearly established, how the latter contributes to growth-promoting pathways is less understood. Macroautophagy, hereafter referred to as autophagy, is a catabolic process that plays a fundamental part in tissue homeostasis (3). We investigated the role of autophagy during bone growth, which is mediated by chondrocyte rate of proliferation, hypertrophic differentiation and extracellular matrix (ECM) deposition in growth plates (4). Here we show that autophagy is induced in growth-plate chondrocytes during post-natal development and regulates the secretion of type II collagen (Col2), the major component of cartilage ECM. Mice lacking the autophagy related gene 7 (Atg7) in chondrocytes experience endoplasmic reticulum storage of type II procollagen (PC2) and defective formation of the Col2 fibrillary network in the ECM. Surprisingly, post-natal induction of chondrocyte autophagy is mediated by the growth factor FGF18 through FGFR4 and JNK-dependent activation of the autophagy initiation complex VPS34-beclin-1. Autophagy is completely suppressed in growth plates from [Fgf18.sup.-/-] embryos, while [Fgf18.sup.+/-] heterozygous and [Fgfr4.sup.-/-] mice fail to induce autophagy during post-natal development and show decreased Col2 levels in the growth plate. Strikingly, the [Fgf18.sup.+/-] and [Fgfr4.sup.-/-] phenotypes can be rescued in vivo by pharmacological activation of autophagy, pointing to autophagy as a novel effector of FGF signalling in bone. These data demonstrate that autophagy is a developmentally regulated process necessary for bone growth, and identify FGF signalling as a crucial regulator of autophagy in chondrocytes., To understand the role of autophagy during bone growth, we analysed the femoral growth plates of transgenic mice that express the green fluorescent protein (GFP)-tagged autophagosome marker MAP1LC3 ([GFP-LC3.sup.tg/+]) (5). [...]

Published
2015

18. Sedlin Controls the ER Export of Procollagen by Regulating the Sar1 Cycle

Author

Venditti, Rossella, Scanu, Tiziana, Santoro, Michele, Di Tullio, Giuseppe, Spaar, Alexander, Gaibisso, Renato, Beznoussenko, Galina V., Mironov, Alexander A., Mironov, Alexander, Zelante, Leopoldo, Piemontese, Maria Rosaria, Notarangelo, Angelo, Malhotra, Vivek, Vertel, Barbara M., Wilson, Cathal, and De Matteis, Maria Antonietta

Published
2012
Full Text
View/download PDF

21. Structural organization and functional properties of miniature DNA insertion sequences in Yersiniae

Author

De Gregorio, Eliana, Silvestro, Giustina, Venditti, Rossella, Carlomagno, Maria Stella, and Di Nocera, Pier Paolo

Subjects
Yersinia -- Genetic aspects, Nucleotide sequence -- Research, DNA -- Research, Genetic research, Biological sciences
Abstract

YPALs (Yersinia palindromic sequences) are miniature DNA insertions scattered along the chromosomes of yersiniae. The spread of these intergenic repeats likely occurred via transposition, as suggested by the presence of target site duplications at their termini and the identification of syntenic chromosomal regions which differ in the presence/absence of YPAL DNA among Yersinia strains. YPALs tend to be inserted closely downstream from the stop codon of flanking genes, and many YPAL targets overlap rho-independent transcriptional terminator-like sequences. This peculiar pattern of insertion supports the hypothesis that most of these repeats are cotranscribed with upstream sequences into mRNAs. YPAL RNAs fold into stable hairpins which may modulate mRNA decay. Accordingly, we found that YPAL-positive transcripts accumulate in Yersinia enterocolitica cells at significantly higher levels than homologous transcripts lacking YPAL sequences in their 3' untranslated region.

Published
2006

24. Correction: VAPB depletion alters neuritogenesis and phosphoinositide balance in motoneuron-like cells: relevance to VAPB-linked amyotrophic lateral sclerosis (doi:10.1242/jcs.220061)

Author

Genevini, Paola, primary, Colombo, Maria Nicol, additional, Venditti, Rossella, additional, Marcuzzo, Stefania, additional, Colombo, Sara Francesca, additional, Bernasconi, Pia, additional, De Matteis, Maria Antonietta, additional, Borgese, Nica, additional, and Navone, Francesca, additional

Published
2019
Full Text
View/download PDF

25. Molecular determinants of ER–Golgi contacts identified through a new FRET–FLIM system

Author

Venditti, Rossella, primary, Rega, Laura Rita, additional, Masone, Maria Chiara, additional, Santoro, Michele, additional, Polishchuk, Elena, additional, Sarnataro, Daniela, additional, Paladino, Simona, additional, D’Auria, Sabato, additional, Varriale, Antonio, additional, Olkkonen, Vesa M., additional, Di Tullio, Giuseppe, additional, Polishchuk, Roman, additional, and De Matteis, Maria Antonietta, additional

Published
2019
Full Text
View/download PDF

26. The activity of Sac1 across ER–TGN contact sites requires the four-phosphate-adaptor-protein-1

Author

Venditti, Rossella, primary, Masone, Maria Chiara, additional, Rega, Laura Rita, additional, Di Tullio, Giuseppe, additional, Santoro, Michele, additional, Polishchuk, Elena, additional, Serrano, Ivan Castello, additional, Olkkonen, Vesa M., additional, Harada, Akihiro, additional, Medina, Diego L., additional, La Montagna, Raffaele, additional, and De Matteis, Maria Antonietta, additional

Published
2019
Full Text
View/download PDF

32. Role of sedlin, a TRAPP complex subunit, in membrane trafficking and in the pathogenesis of Spondyleopyphiseal Dysplasia Tarda

Author

Venditti, Rossella

Abstract

Genetic defects occurring in the sedlin gene, a conserved component of TRAPP complex, cause Spondyloepiphyseal Dysplasia Tarda (SEDT), a rare progressive condition characterised by impaired chondrogenesis resulting in short stature, flattening of the vertebrae, and premature osteoarthritis. The role of sedlin in the pathogenesis of SEDT disease so far is still unknown. Prompted by the consideration that sedlin is ubiquitously expressed but that sedlin mutations cause cartilaginous-restricted dysfunctions, I hypothesized that sedlin might exert a role in membrane trafficking generally but in particular in the transport of chondrocyte- specific cargoes, such as type II procollagen (PCII). This hypothesis was reinforced by the fact that mutations in PCII give rise to autosomal dominant forms of spondyloepiphiseal dysplasia. I tested this hypothesis by analyzing the involvement of sedlin in the transport of different classes of secretory cargoes and found that sedlin is selectively required for PCII to exit the ER, while it is not essential for ER exit of small soluble and membrane-associated cargoes. I have also identified the molecular mechanism underlying this role of sedlin in its ability to bind the GTPase Sarl and to control the membrane-cytosol cycle of Sarl itself and of the COPIl coat complex at the level of the ER exit sites. Sedlin depletion and/or mutation in SEDT patients slows down the Sar1 cycle and prolongs the membrane association of Sar1-GTP at the ER exit sites, thus inducing constriction and premature fission of nascent carriers which fail to incorporate the large PC protofibrils but are still competent for smaller secretory cargoes. All together these findings provide new insights not only into understanding the role of sedlin but also shed new light on the molecular mechanisms underlying the onset of the SEDT disease.

Published
2012

34. Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB

Author

Medina, Diego L., primary, Di Paola, Simone, additional, Peluso, Ivana, additional, Armani, Andrea, additional, De Stefani, Diego, additional, Venditti, Rossella, additional, Montefusco, Sandro, additional, Scotto-Rosato, Anna, additional, Prezioso, Carolina, additional, Forrester, Alison, additional, Settembre, Carmine, additional, Wang, Wuyang, additional, Gao, Qiong, additional, Xu, Haoxing, additional, Sandri, Marco, additional, Rizzuto, Rosario, additional, De Matteis, Maria Antonietta, additional, and Ballabio, Andrea, additional

Published
2015
Full Text
View/download PDF

40. A novel class of small repetitive DNA sequences in Enterococcus faecalis.

Author

Venditti, Rossella, de Gregorio, Eliana, Silvestro, Giustina, Bertocco, Tullia, Salza, Maria Francesca, Zarrilli, Raffaele, and Di Nocera, Pier Paolo

Subjects
*ENTEROCOCCUS faecalis, *GRAM-positive bacteria, *NUCLEOTIDE sequence, *POLYMERASE chain reaction, *POLYMERIZATION, *MICROBIOLOGY
Abstract

The structural organization of nterococcus ecalis epeats (EFAR) is described, palindromic DNA sequences identified in the genome of the Enterococcus faecalis V583 strain by in silico analyses. EFAR are a novel type of miniature insertion sequences, which vary in size from 42 to 650 bp. Length heterogeneity results from the variable assembly of 16 different sequence types. Most elements measure 170 bp, and can fold into peculiar L-shaped structures resulting from the folding of two independent stem-loop structures (SLSs). Homologous chromosomal regions lacking or containing EFAR sequences were identified by PCR among 20 E. faecalis clinical isolates of different genotypes. Sequencing of a representative set of ‘empty’ sites revealed that 24–37 bp-long sequences, unrelated to each other but all able to fold into SLSs, functioned as targets for the integration of EFAR. In the process, most of the SLS had been deleted, but part of the targeted stems had been retained at EFAR termini. [ABSTRACT FROM AUTHOR]

Published
2007
Full Text
View/download PDF

41. Role of sedlin, a TRAPP complex subunit, in membrane trafficking and in the pathogenesis of Spondyleopyphiseal Dysplasia Tarda

Author

Venditti, Rossella and Venditti, Rossella

Abstract

Genetic defects occurring in the sedlin gene, a conserved component of TRAPP complex, cause Spondyloepiphyseal Dysplasia Tarda (SEDT), a rare progressive condition characterised by impaired chondrogenesis resulting in short stature, flattening of the vertebrae, and premature osteoarthritis. The role of sedlin in the pathogenesis of SEDT disease so far is still unknown. Prompted by the consideration that sedlin is ubiquitously expressed but that sedlin mutations cause cartilaginous-restricted dysfunctions, I hypothesized that sedlin might exert a role in membrane trafficking generally but in particular in the transport of chondrocyte- specific cargoes, such as type II procollagen (PCII). This hypothesis was reinforced by the fact that mutations in PCII give rise to autosomal dominant forms of spondyloepiphiseal dysplasia. I tested this hypothesis by analyzing the involvement of sedlin in the transport of different classes of secretory cargoes and found that sedlin is selectively required for PCII to exit the ER, while it is not essential for ER exit of small soluble and membrane-associated cargoes. I have also identified the molecular mechanism underlying this role of sedlin in its ability to bind the GTPase Sarl and to control the membrane-cytosol cycle of Sarl itself and of the COPIl coat complex at the level of the ER exit sites. Sedlin depletion and/or mutation in SEDT patients slows down the Sar1 cycle and prolongs the membrane association of Sar1-GTP at the ER exit sites, thus inducing constriction and premature fission of nascent carriers which fail to incorporate the large PC protofibrils but are still competent for smaller secretory cargoes. All together these findings provide new insights not only into understanding the role of sedlin but also shed new light on the molecular mechanisms underlying the onset of the SEDT disease.

42. Role of sedlin, a TRAPP complex subunit, in membrane trafficking and in the pathogenesis of Spondyleopyphiseal Dysplasia Tarda

Author

Venditti, Rossella and Venditti, Rossella

Abstract

Genetic defects occurring in the sedlin gene, a conserved component of TRAPP complex, cause Spondyloepiphyseal Dysplasia Tarda (SEDT), a rare progressive condition characterised by impaired chondrogenesis resulting in short stature, flattening of the vertebrae, and premature osteoarthritis. The role of sedlin in the pathogenesis of SEDT disease so far is still unknown. Prompted by the consideration that sedlin is ubiquitously expressed but that sedlin mutations cause cartilaginous-restricted dysfunctions, I hypothesized that sedlin might exert a role in membrane trafficking generally but in particular in the transport of chondrocyte- specific cargoes, such as type II procollagen (PCII). This hypothesis was reinforced by the fact that mutations in PCII give rise to autosomal dominant forms of spondyloepiphiseal dysplasia. I tested this hypothesis by analyzing the involvement of sedlin in the transport of different classes of secretory cargoes and found that sedlin is selectively required for PCII to exit the ER, while it is not essential for ER exit of small soluble and membrane-associated cargoes. I have also identified the molecular mechanism underlying this role of sedlin in its ability to bind the GTPase Sarl and to control the membrane-cytosol cycle of Sarl itself and of the COPIl coat complex at the level of the ER exit sites. Sedlin depletion and/or mutation in SEDT patients slows down the Sar1 cycle and prolongs the membrane association of Sar1-GTP at the ER exit sites, thus inducing constriction and premature fission of nascent carriers which fail to incorporate the large PC protofibrils but are still competent for smaller secretory cargoes. All together these findings provide new insights not only into understanding the role of sedlin but also shed new light on the molecular mechanisms underlying the onset of the SEDT disease.

43. <scp>ER</scp> exit sites take the strain

Author

Rossella Venditti, Maria Antonietta De Matteis, De Matteis, Maria Antonietta, and Venditti, Rossella

Subjects
Protein Transport, General Immunology and Microbiology, General Neuroscience, Golgi Apparatu, Endoplasmic Reticulum, Molecular Biology, General Biochemistry, Genetics and Molecular Biology, Monomeric GTP-Binding Proteins
Abstract

Cells are able to adapt their growth to external mechanical strain. A recent study by Phuyal et al (2022) has shown that these responses depend on the heterodimerization of two small GTPases.

Published
2022
Full Text
View/download PDF

44. Distinct changes in endosomal composition promote NLRP3 inflammasome activation

Author

Zhirong Zhang, Rossella Venditti, Li Ran, Zengzhen Liu, Karl Vivot, Annette Schürmann, Juan S. Bonifacino, Maria Antonietta De Matteis, Romeo Ricci, Zhang, Zhirong, Venditti, Rossella, Ran, Li, Liu, Zengzhen, Vivot, Karl, Schürmann, Annette, Bonifacino, Juan S, De Matteis, Maria Antonietta, and Ricci, Romeo

Subjects
Immunology, Immunology and Allergy
Abstract

Inflammasome complexes are pivotal in the innate immune response. The NLR family pyrin domain containing protein 3 (NLRP3) inflammasome is activated in response to a broad variety of cellular stressors. However, a primary and converging sensing mechanism by the NLRP3 receptor initiating inflammasome assembly remains ill defined. Here, we demonstrate that NLRP3 inflammasome activators primarily converge on disruption of endoplasmic reticulum–endosome membrane contact sites (EECS). This defect causes endosomal accumulation of phosphatidylinositol 4-phosphate (PI4P) and a consequent impairment of endosome-to-trans-Golgi network trafficking (ETT), necessary steps for endosomal recruitment of NLRP3 and subsequent inflammasome activation. Lowering endosomal PI4P levels prevents endosomal association of NLRP3 and inhibits inflammasome activation. Disruption of EECS or ETT is sufficient to enhance endosomal PI4P levels, to recruit NLRP3 to endosomes and to potentiate NLRP3 inflammasome activation. Mice with defects in ETT in the myeloid compartment are more susceptible to lipopolysaccharide-induced sepsis. Our study thus identifies a distinct cellular mechanism leading to endosomal NLRP3 recruitment and inflammasome activation.

Published
2022

45. The role of NSP6 in the biogenesis of the SARS-CoV-2 replication organelle

Author

Simona Ricciardi, Andrea Maria Guarino, Laura Giaquinto, Elena V. Polishchuk, Michele Santoro, Giuseppe Di Tullio, Cathal Wilson, Francesco Panariello, Vinicius C. Soares, Suelen S. G. Dias, Julia C. Santos, Thiago M. L. Souza, Giovanna Fusco, Maurizio Viscardi, Sergio Brandi, Patrícia T. Bozza, Roman S. Polishchuk, Rossella Venditti, Maria Antonietta De Matteis, Ricciardi, Simona, Guarino, Andrea Maria, Giaquinto, Laura, Polishchuk, Elena V, Santoro, Michele, Di Tullio, Giuseppe, Wilson, Cathal, Panariello, Francesco, Soares, Vinicius C, Dias, Suelen S G, Santos, Julia C, Souza, Thiago M L, Fusco, Giovanna, Viscardi, Maurizio, Brandi, Sergio, Bozza, Patrícia T, Polishchuk, Roman S, Venditti, Rossella, and De Matteis, Maria Antonietta

Subjects
Multidisciplinary, SARS-CoV-2, rab GTP-Binding Proteins, COVID-19, Coronavirus Nucleocapsid Proteins, Humans, Lipid Droplets, Viral Nonstructural Proteins, Carrier Proteins, Endoplasmic Reticulum, Virus Replication, Article, Cell Line
Abstract

SARS-CoV-2, like other coronaviruses, builds a membrane-bound replication organelle (RO) to enable RNA replication(1). The SARS-CoV-2 RO is composed of double membrane vesicles (DMVs) tethered to the endoplasmic reticulum (ER) by thin membrane connectors(2), but the viral proteins and the host factors involved are currently unknown. Here we identify the viral non-structural proteins (NSPs) that generate the SARS-CoV-2 RO. NSP3 and NSP4 generate the DMVs while NSP6, through oligomerization and an amphipathic helix, zippers ER membranes and establishes the connectors. The NSP6ΔSGF mutant, which arose independently in the α, β, γ, η, ι and λ variants of SARS-CoV-2, behaves as a gain-of-function mutant with a higher ER-zippering activity. We identified three main roles for NSP6: to act as a filter in RO-ER communication allowing lipid flow but restricting access of ER luminal proteins to the DMVs, to position and organize DMV clusters, and to mediate contact with lipid droplets (LDs) via the LD-tethering complex DFCP1-Rab18. NSP6 thus acts as an organizer of DMV clusters and can provide a selective track to refurbish them with LD-derived lipids. Importantly, both properly formed NSP6 connectors and LDs are required for SARS-CoV-2 replication. Our findings, uncovering the biological activity of NSP6 of SARS-CoV-2 and of other coronaviruses, have the potential to fuel the search for broad antiviral agents.

Published
2022

46. The activity of Sac1 across ER–TGN contact sites requires the four-phosphate-adaptor-protein-1

Author

Elena Polishchuk, Akihiro Harada, Vesa M. Olkkonen, Raffaele La Montagna, Diego L. Medina, Michele Santoro, Giuseppe Di Tullio, Maria Chiara Masone, Rossella Venditti, Iván Castelló Serrano, Maria Antonietta De Matteis, Laura Rita Rega, Venditti, Rossella, Masone, Maria Chiara, Rega, Laura Rita, Di Tullio, Giuseppe, Santoro, Michele, Polishchuk, Elena, Serrano, Ivan Castello, Olkkonen, Vesa M, Harada, Akihiro, Medina, Diego, La Montagna, Raffaele, De Matteis, Maria Antonietta, Medicum, Department of Anatomy, Faculty of Medicine, and University of Helsinki

Subjects
Phosphoric monoester hydrolases, Phosphatidylinositol 4-phosphate, Phosphatase, PROTEIN, Biology, 03 medical and health sciences, symbols.namesake, chemistry.chemical_compound, 0302 clinical medicine, Report, BINDING, MULTIPLE, Secretion, TRAFFICKING, Research Articles, 030304 developmental biology, 0303 health sciences, Kinase, GOLGI, Signal transducing adaptor protein, LOCALIZATION, Cell Biology, Golgi apparatus, In vitro, PHOSPHATASE SAC1, TRANSPORT, EXPORT, Cell biology, chemistry, symbols, PHOSPHATIDYLINOSITOL-4-PHOSPHATE, 1182 Biochemistry, cell and molecular biology, 3111 Biomedicine, 030217 neurology & neurosurgery
Abstract

Venditti et al. identify FAPP1 as a new determinant of ER–trans-Golgi network contacts that interacts with the phosphoinositide phosphatase Sac1 and promotes its phosphatase activity. The results suggest that, by controlling PI4P levels, FAPP1 acts as a gatekeeper of cargo Golgi exit., Phosphatidylinositol-4-phosphate (PI4P), a phosphoinositide with key roles in the Golgi complex, is made by Golgi-associated phosphatidylinositol-4 kinases and consumed by the 4-phosphatase Sac1 that, instead, is an ER membrane protein. Here, we show that the contact sites between the ER and the TGN (ERTGoCS) provide a spatial setting suitable for Sac1 to dephosphorylate PI4P at the TGN. The ERTGoCS, though necessary, are not sufficient for the phosphatase activity of Sac1 on TGN PI4P, since this needs the phosphatidyl-four-phosphate-adaptor-protein-1 (FAPP1). FAPP1 localizes at ERTGoCS, interacts with Sac1, and promotes its in-trans phosphatase activity in vitro. We envision that FAPP1, acting as a PI4P detector and adaptor, positions Sac1 close to TGN domains with elevated PI4P concentrations allowing PI4P consumption. Indeed, FAPP1 depletion induces an increase in TGN PI4P that leads to increased secretion of selected cargoes (e.g., ApoB100), indicating that FAPP1, by controlling PI4P levels, acts as a gatekeeper of Golgi exit.

Published
2019

47. ER-Golgi membrane contact sites

Author

Maria Antonietta De Matteis, Rossella Venditti, Maria Chiara Masone, Venditti, Rossella, Masone, Maria Chiara, and De Matteis, Maria Antonietta

Subjects
membrane contact site, phosphatidylinositol, Endoplasmic Reticulum, Phosphatidylinositols, Biochemistry, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Organelle, Homeostasis, Humans, Er golgi, Eye Proteins, 030304 developmental biology, 0303 health sciences, golgi apparatu, Chemistry, Endoplasmic reticulum, Calcium-Binding Proteins, Membrane Proteins, Intracellular Membranes, Golgi apparatus, Cell biology, Protein Transport, Membrane, Microscopy, Fluorescence, symbols, Microscopy, Electron, Scanning, Calcium, Carrier Proteins, Plant lipid transfer proteins, 030217 neurology & neurosurgery, Function (biology), trans-Golgi Network
Abstract

Membrane contact sites (MCSs) are sites where the membranes of two different organelles come into close apposition (10–30 nm). Different classes of proteins populate MCSs including factors that act as tethers between the two membranes, proteins that use the MCSs for their function (mainly lipid or ion exchange), and regulatory proteins and enzymes that can act in trans across the MCSs. The ER-Golgi MCSs were visualized by electron microscopists early in the sixties but have remained elusive for decades due to a lack of suitable methodological approaches. Here we report recent progress in the study of this class of MCSs that has led to the identification of their main morphological features and of some of their components and roles. Among these, lipid transfer proteins and lipid exchange have been the most studied and understood so far. However, many unknowns remain regarding their regulation and their role in controlling key TGN functions such as sorting and trafficking as well as their relevance in physiological and pathological conditions.

Published
2019

48. Molecular determinants of ER–Golgi contacts identified through a new FRET–FLIM system

Author

Roman S. Polishchuk, Antonio Varriale, Daniela Sarnataro, Giuseppe Di Tullio, Maria Chiara Masone, Simona Paladino, Sabato D'Auria, Rossella Venditti, Elena Polishchuk, Vesa M. Olkkonen, Michele Santoro, Maria Antonietta De Matteis, Laura Rita Rega, Venditti, Rossella, Rega, Laura Rita, Masone, Maria Chiara, Santoro, Michele, Polishchuk, Elena, Sarnataro, Daniela, Paladino, Simona, D'Auria, Sabato, Varriale, Antonio, Olkkonen, Vesa M, Di Tullio, Giuseppe, Polishchuk, Roman, De Matteis, Maria Antonietta, Medicum, Faculty of Medicine, Department of Anatomy, and University of Helsinki

Subjects
PROTEINS, ENDOPLASMIC-RETICULUM, Biology, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, BINDING, TRAFFICKING, LIPID-TRANSFER, PHOSPHATIDYLSERINE, 030304 developmental biology, Ceramide Transfer Protein, 0303 health sciences, Endoplasmic reticulum, Cell Biology, VAPB, Golgi apparatus, biosensors, TRANSPORT, Cell biology, Förster resonance energy transfer, Membrane protein, Oxysterol binding, PLASMA-MEMBRANE, symbols, VAP, 1182 Biochemistry, cell and molecular biology, lipids (amino acids, peptides, and proteins), 3111 Biomedicine, INTERACTOME, Plant lipid transfer proteins, 030217 neurology & neurosurgery
Abstract

ER–TGN contact sites (ERTGoCS) have been visualized by electron microscopy, but their location in the crowded perinuclear area has hampered their analysis via optical microscopy as well as their mechanistic study. To overcome these limits we developed a FRET-based approach and screened several candidates to search for molecular determinants of the ERTGoCS. These included the ER membrane proteins VAPA and VAPB and lipid transfer proteins possessing dual (ER and TGN) targeting motifs that have been hypothesized to contribute to the maintenance of ERTGoCS, such as the ceramide transfer protein CERT and several members of the oxysterol binding proteins. We found that VAP proteins, OSBP1, ORP9, and ORP10 are required, with OSBP1 playing a redundant role with ORP9, which does not involve its lipid transfer activity, and ORP10 being required due to its ability to transfer phosphatidylserine to the TGN. Our results indicate that both structural tethers and a proper lipid composition are needed for ERTGoCS integrity.

Published
2019
Full Text
View/download PDF

49. VAPB depletion alters neuritogenesis and phosphoinositide balance in motoneuron-like cells: relevance to VAPB-linked ALS

Author

Maria Nicol Colombo, Francesca Navone, Maria Antonietta De Matteis, Stefania Marcuzzo, Paola Genevini, Pia Bernasconi, Rossella Venditti, Nica Borgese, Sara Francesca Colombo, Genevini, Paola, Colombo, Maria Nicol, Venditti, Rossella, Marcuzzo, Stefania, Colombo, Sara Francesca, Bernasconi, Pia, De Matteis, Maria Antonietta, Borgese, Nica, and Navone, Francesca

Subjects
Phosphatidylinositol-4-phosphate, Phosphatidylinositol 4-phosphate, Mutant, Biology, Neurodegenerative disease, 03 medical and health sciences, symbols.namesake, chemistry.chemical_compound, 0302 clinical medicine, medicine, Amyotrophic lateral sclerosis, Neuritogenesi, 030304 developmental biology, 0303 health sciences, Endoplasmic reticulum membrane, Kinase, NSC34 cell, Cell Biology, Golgi apparatus, VAPB, medicine.disease, Cell biology, chemistry, Endo-lysosome, symbols, Haploinsufficiency, 030217 neurology & neurosurgery
Abstract

VAPB and VAPA are ubiquitously expressed endoplasmic reticulum membrane proteins that play key roles in lipid exchange at membrane contact sites. A mutant, aggregation-prone, form of VAPB (P56S) is linked to a dominantly inherited form of amyotrophic lateral sclerosis; however, it has been unclear whether its pathogenicity is due to toxic gain of function, to negative dominance, or simply to insufficient levels of the wild-type protein produced from a single allele (haploinsufficiency). To investigate whether reduced levels of functional VAPB, independently from the presence of the mutant form, affect the physiology of mammalian motoneuron-like cells, we generated NSC34 clones, from which VAPB was partially or nearly completely depleted. VAPA levels, determined to be over fourfold higher than those of VAPB in untransfected cells, were unaffected. Nonetheless, cells with even partially depleted VAPB showed an increase in Golgi- and acidic vesicle-localized phosphatidylinositol-4-phosphate (PI4P) and reduced neurite extension when induced to differentiate. Conversely, the PI4 kinase inhibitors PIK93 and IN-10 increased neurite elongation. Thus, for long-term survival, motoneurons might require the full dose of functional VAPB, which may have unique function(s) that VAPA cannot perform.

Published
2019
Full Text
View/download PDF

50. Cellular Assays for Drug Discovery in Genetic Disorders of Intracellular Trafficking

Author

Rossella Venditti, Cathal Wilson, Mariella Vicinanza, Maria Antonietta De Matteis, DE MATTEIS, Maria Antonietta, Vicinanza, Mariella, Venditti, Rossella, and Wilson, Cathal

Subjects
Intracellular Membrane, Cell, Genetic disease, Membrane trafficking, Biology, Genetic, Drug Discovery, Organelle, Genetics, medicine, Animals, Humans, Pharmacological approach, Molecular Biology, Genetics (clinical), Animal, Drug discovery, High-content screening, Genetic Diseases, Inborn, Intracellular Membranes, Cell biology, Transport protein, Protein Transport, medicine.anatomical_structure, Cell-based assay, Organelle biogenesis, Intracellular, Function (biology), Human
Abstract

Intracellular membrane trafficking is essential for organelle biogenesis, structure, and function; the exchange of material between organelles; and communication between the cell and its external environment. Genetic disorders affecting intracellular trafficking can lead to a variety of human diseases, but specific therapies for these diseases are notably lacking. In this article, we focus on how current knowledge about genetic disorders that affect intracellular trafficking can be used to develop strategies for cell-based assays in order to identify drugs using high-content screening approaches.

Published
2013
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results