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2. Genetic code expansion, click chemistry, and light-activated PI3K reveal details of membrane protein trafficking downstream of receptor tyrosine kinases

Author

Duk-Su Koh, Anastasiia Stratiievska, Subhashis Jana, Shauna C Otto, Teresa M Swanson, Anthony Nhim, Sara Carlson, Marium Raza, Ligia Araujo Naves, Eric N Senning, Ryan A Mehl, and Sharona E Gordon

Subjects
membrane protein, trafficking, click chemistry, Medicine, Science, Biology (General), QH301-705.5
Abstract

Ligands such as insulin, epidermal growth factor, platelet-derived growth factor, and nerve growth factor (NGF) initiate signals at the cell membrane by binding to receptor tyrosine kinases (RTKs). Along with G-protein-coupled receptors, RTKs are the main platforms for transducing extracellular signals into intracellular signals. Studying RTK signaling has been a challenge, however, due to the multiple signaling pathways to which RTKs typically are coupled, including MAP/ERK, PLCγ, and Class 1A phosphoinositide 3-kinases (PI3K). The multi-pronged RTK signaling has been a barrier to isolating the effects of any one downstream pathway. Here, we used optogenetic activation of PI3K to decouple its activation from other RTK signaling pathways. In this context, we used genetic code expansion to introduce a click chemistry noncanonical amino acid into the extracellular side of membrane proteins. Applying a cell-impermeant click chemistry fluorophore allowed us to visualize delivery of membrane proteins to the plasma membrane in real time. Using these approaches, we demonstrate that activation of PI3K, without activating other pathways downstream of RTK signaling, is sufficient to traffic the TRPV1 ion channels and insulin receptors to the plasma membrane.

Published
2024
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11. A specific brain network for a social map in the human brain

Author

Lu Zhang, Ping Chen, Matthew Schafer, Senning Zheng, Lixiang Chen, Shuai Wang, Qunjun Liang, Qing Qi, Yichen Zhang, and Ruiwang Huang

Subjects
Medicine, Science
Abstract

Abstract Individuals use social information to guide social interactions and to update relationships along multiple social dimensions. However, it is unclear what neural basis underlies this process of abstract “social navigation”. In the current study, we recruited twenty-nine participants who performed a choose-your-own-adventure game in which they interacted with fictional characters during fMRI scanning. Using a whole-brain GLM approach, we found that vectors encoding two-dimensional information about the relationships predicted BOLD responses in the hippocampus and the precuneus, replicating previous work. We also explored whether these geometric representations were related to key brain regions previously identified in physical and abstract spatial navigation studies, but we did not find involvement of the entorhinal cortex, parahippocampal gyrus or the retrosplenial cortex. Finally, we used psychophysiological interaction analysis and identified a network of regions that correlated during participants’ decisions, including the left posterior hippocampus, precuneus, dorsolateral prefrontal cortex (dlPFC), and the insula. Our findings suggest a brain network for social navigation in multiple abstract, social dimensions that includes the hippocampus, precuneus, dlPFC, and insula.

Published
2022
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14. Dynamic Causal Modelling of Hierarchical Planning

Author

Qunjun Liang, Jinhui Li, Senning Zheng, Jiajun Liao, and Ruiwang Huang

Subjects
Dynamic Causal Modelling (DCM), Parametric Empirical Bayes (PEB), fMRI, neural architecture, individual difference, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Hierarchical planning (HP) is a strategy that optimizes the planning by storing the steps towards the goal (lower-level planning) into subgoals (higher-level planning). In the framework of model-based reinforcement learning, HP requires the computation through the transition value between higher-level hierarchies. Previous study identified the dmPFC, PMC and SPL were involved in the computation process of HP respectively. However, it is still unclear about how these regions interaction with each other to support the computation in HP, which could deepen our understanding about the implementation of plan algorithm in hierarchical environment. To address this question, we conducted an fMRI experiment using a virtual subway navigation task. We identified the activity of the dmPFC, premotor cortex (PMC) and superior parietal lobe (SPL) with general linear model (GLM) in HP. Then, Dynamic Causal Modelling (DCM) was performed to quantify the influence of the higher- and lower-planning on the connectivity between the brain areas identified by the GLM. The strongest modulation effect of the higher-level planning was found on the dmPFC→right PMC connection. Furthermore, using Parametric Empirical Bayes (PEB), we found the modulation of higher-level planning on the dmPFC→right PMC and right PMC→SPL connections could explain the individual difference of the response time. We conclude that the dmPFC-related connectivity takes the response to the higher-level planning, while the PMC acts as the bridge between the higher-level planning to behavior outcome.

Published
2022
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16. Cross-layer Energy-Efficiency Optimization of Packet Based Wireless MIMO Communication Systems

Author

Senning, Christian, Karakonstantis, Georgios, and Burg, Andreas

Subjects
Computer Science - Networking and Internet Architecture
Abstract

Energy in today's short-range wireless communication is mostly spent on the analog- and digital hardware rather than on radiated power. Hence, purely information-theoretic considerations fail to achieve the lowest energy per information bit and the optimization process must carefully consider the overall transceiver. In this paper, we propose to perform cross-layer optimization, based on an energy-aware rate adaptation scheme combined with a physical layer that is able to properly adjust its processing effort to the data rate and the channel conditions to minimize the energy consumption per information bit. This energy proportional behavior is enabled by extending the classical system modes with additional configuration parameters at the various layers. Fine grained models of the power consumption of the hardware are developed to provide awareness of the physical layer capabilities to the medium access control layer. The joint application of the proposed energy-aware rate adaptation and modifications to the physical layer of an IEEE 802.11n system, improves energy-efficiency (averaged over many noise and channel realizations) in all considered scenarios by up to 44%., Comment: Accepted for publication in The Journal of Signal Processing Systems

Published
2015

22. Impact of Overweight and Obesity on Disease Outcome in the Pediatric Swiss Inflammatory Bowel Disease Cohort

Author

von Graffenried, Thea, Schoepfer, Alain M., Rossel, Jean-Benoit, Greuter, Thomas, Safroneeva, Ekaterina, Godat, Sébastien, Henchoz, Sarah, Vavricka, Stephan R., Sokollik, Christiane, Spalinger, Johannes, Braegger, Christian P., Nydegger, Andreas, Abdelrahman, Karim, Ademi, Gentiana, Aepli, Patrick, Thomas, Amman, Anderegg, Claudia, Antonino, Anca-Teodora, Archanioti, Eva, Arrigoni, Eviano, de Jong, Diana Bakker, Balsiger, Bruno, Bastürk, Polat, Bauerfeind, Peter, Becocci, Andrea, Belli, Dominique, Bengoa, José M., Biedermann, Luc, Binek, Janek, Blattmann, Mirjam, Boehm, Stephan, Boldanova, Tujana, Borovicka, Jan, Braegger, Christian P., Brand, Stephan, Brügger, Lukas, Brunner, Simon, Bühr, Patrick, Burnand, Bernard, Burk, Sabine, Burri, Emanuel, Buyse, Sophie, Cao, Dahlia-Thao, Carstens, Ove, Criblez, Dominique H., Cunningham, Sophie, D’Angelo, Fabrizia, de Saussure, Philippe, Degen, Lukas, Delarive, Joakim, Doerig, Christopher, Dora, Barbara, Drerup, Susan, Egger, Mara, El-Wafa, Ali, Engelmann, Matthias, Felley, Christian, Fliegner, Markus, Fournier, Nicolas, Fraga, Montserrat, Franc, Yannick, Frei, Pascal, Frei, Remus, Fried, Michael, Froehlich, Florian, Furlano, Raoul Ivano, Garzoni, Luca, Geyer, Martin, Girard, Laurent, Girardin, Marc, Golay, Delphine, Good, Ignaz, Bigler, Ulrike Graf, Gysi, Beat, Haarer, Johannes, Halama, Marcel, Haldemann, Janine, Heer, Pius, Heimgartner, Benjamin, Helbling, Beat, Hengstler, Peter, Herzog, Denise, Hess, Cyrill, Heyland, Klaas, Hinterleitner, Thomas, Hirschi, Claudia, Hruz, Petr, Juillerat, Pascal, Khalid-de Bakker, Carolina, Kayser, Stephan, Keller, Céline, Knellwolf, Christina, Knoblauch, Christoph, Köhler, Henrik, Koller, Rebekka, Krieger, Claudia, Künzler, Patrizia, Kusche, Rachel, Lehmann, Frank Serge, Macpherson, Andrew, Maillard, Michel H., Manz, Michael, Marot, Astrid, Meier, Rémy, Meyenberger, Christa, Meyer, Pamela, Michetti, Pierre, Misselwitz, Benjamin, Mosler, Patrick, Mottet, Christian, Müller, Christoph, Müllhaupt, Beat, Musso, Leilla, Neagu, Michaela, Nichita, Cristina, Niess, Jan, Nydegger, Andreas, Obialo, Nicole, Ollo, Diana, Oropesa, Cassandra, Peter, Ulrich, Peternac, Daniel, Petit, Laetitia Marie, Pittet, Valérie, Pohl, Daniel, Porzner, Marc, Preissler, Claudia, Raschle, Nadia, Rentsch, Ronald, Restellini, Alexandre, Restellini, Sophie, Richterich, Jean-Pierre, Ris, Frederic, Risti, Branislav, Ritz, Marc Alain, Rogler, Gerhard, Röhrich, Nina, Rossel, Jean-Benoît, Rueger, Vanessa, Rusticeanu, Monica, Sagmeister, Markus, Saner, Gaby, Sauter, Bernhard, Sawatzki, Mikael, Scharl, Michael, Schelling, Martin, Schibli, Susanne, Schlauri, Hugo, Schluckebier, Dominique, Schmid, Daniela, Schmid, Sybille, Schnegg, Jean-François, Schoepfer, Alain, Seematter, Vivianne, Seibold, Frank, Seirafi, Mariam, Semadeni, Gian-Marco, Senning, Arne, Sokollik, Christiane, Sommer, Joachim, Spalinger, Johannes, Spangenberger, Holger, Stadler, Philippe, Staub, Peter, Staudenmann, Dominic, Stenz, Volker, Steuerwald, Michael, Straumann, Alex, Stulz, Andreas, Sulz, Michael, Tatu, Aurora, Tempia-Caliera, Michela, Thorens, Joël, Truninger, Kaspar, Tutuian, Radu, Urfer, Patrick, Vavricka, Stephan, Viani, Francesco, Vögtlin, Jürg, Von Känel, Roland, Vouillamoz, Dominique, Vulliamy, Rachel, Wiesel, Paul, Wiest, Reiner, Wöhrle, Stefanie, Zamora, Samuel, Zander, Silvan, Zeitz, Jonas, and Zimmermann, Dorothee

Published
2022
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23. Disrupted Brain Connectivity Networks in Aphasia Revealed by Resting-State fMRI

Author

Xiaoyun Chen, Liting Chen, Senning Zheng, Hong Wang, Yanhong Dai, Zhuoming Chen, and Ruiwang Huang

Subjects
aphasia, cognitive impairment, topological properties, functional MRI, stroke, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Aphasia is characterized by the disability of spontaneous conversation, listening, understanding, retelling, naming, reading, or writing. However, the neural mechanisms of language damage after stroke are still under discussion. This study aimed to investigate the global and nodal characterization of the functional networks in patients with aphasic stroke based on resting-state functional MRI (fMRI). Twenty-four right-handed patients with aphasia after stroke and 19 healthy controls (HC) underwent a 3-TfMRI scan. A whole-brain large-scale functional connectivity network was then constructed based on Power's atlas of 264 functional regions of interest, and the global and nodal topological properties of these networks were analyzed using graph theory approaches. The results showed that patients with aphasia had decreased in small-worldness (sigma), normalized clustering coefficient (gamma), and local efficiency (Eloc) values. Furthermore, Eloc was positively correlated with language ability, retelling, naming, and listening comprehension in patients with aphasia. Patients with aphasia also had decreased nodal degree and decreased nodal efficiency in the left postcentral gyrus, central opercular cortex, and insular cortex. Our results suggest that the global and local topology attributes were altered by injury in patients with aphasic stroke. We argue that the local efficiency of brain networks might be used as a potential indicator of basic speech function in patients with aphasia.

Published
2021
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24. Human spatial navigation: Neural representations of spatial scales and reference frames obtained from an ALE meta-analysis

Author

Jinhui Li, Ruibin Zhang, Siqi Liu, Qunjun Liang, Senning Zheng, Xianyou He, and Ruiwang Huang

Subjects
Vista space, Environmental space, Allocentric reference frame, Egocentric reference frame, Spatial navigation, Meta-analytic connectivity modeling, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Humans use different spatial reference frames (allocentric or egocentric) to navigate successfully toward their destination in different spatial scale spaces (environmental or vista). However, it remains unclear how the brain represents different spatial scales and different spatial reference frames. Thus, we conducted an activation likelihood estimation (ALE) meta-analysis of 47 fMRI articles involving human spatial navigation. We found that both the environmental and vista spaces activated the parahippocampal place area (PPA), retrosplenial complex (RSC), and occipital place area in the right hemisphere. The environmental space showed stronger activation than the vista space in the occipital and frontal regions. No brain region exhibited stronger activation for the vista than the environmental space. The allocentric and egocentric reference frames activated the bilateral PPA and right RSC. The allocentric frame showed more stronger activations than the egocentric frame in the right culmen, left middle frontal gyrus, and precuneus. No brain region displayed stronger activation for the egocentric than the allocentric navigation. Our findings suggest that navigation in different spatial scale spaces can evoke specific and common brain regions, and that the brain regions representing spatial reference frames are not absolutely separated.

Published
2021
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25. Differences in Outcomes Reported by Patients With Inflammatory Bowel Diseases vs Their Health Care Professionals

Author

Anderegg, Claudia, Bauerfeind, Peter, Beglinger, Christoph, Begré, Stefan, Belli, Dominique, Bengoa, José M., Biedermann, Luc, Bigler, Beat, Binek, Janek, Blattmann, Mirjam, Boehm, Stephan, Borovicka, Jan, Braegger, Christian P., Brunner, Nora, Bühr, Patrick, Burnand, Bernard, Burri, Emanuel, Buyse, Sophie, Cremer, Matthias, Criblez, Dominique H., de Saussure, Philippe, Degen, Lukas, Delarive, Joakim, Doerig, Christopher, Dora, Barbara, Dorta, Gian, Egger, Mara, Ehmann, Tobias, El-Wafa, Ali, Engelmann, Matthias, Ezri, Jessica, Felley, Christian, Fliegner, Markus, Fournier, Nicolas, Fraga, Montserrat, Frei, Pascal, Frei, Remus, Fried, Michael, Froehlich, Florian, Funk, Christian, Furlano, Raoul Ivano, Gallot-Lavallée, Suzanne, Geyer, Martin, Girardin, Marc, Golay, Delphine, Grandinetti, Tanja, Gysi, Beat, Haack, Horst, Haarer, Johannes, Helbling, Beat, Hengstler, Peter, Herzog, Denise, Hess, Cyrill, Heyland, Klaas, Hinterleitner, Thomas, Hiroz, Philippe, Hirschi, Claudia, Hruz, Petr, Iwata, Rika, Jost, Res, Juillerat, Pascal, Keller, Céline, Knellwolf, Christina, Knoblauch, Christoph, Köhler, Henrik, Koller, Rebekka, Krieger-Grübel, Claudia, Kullak-Ublick, Gerd, Künzler, Patrizia, Landolt, Markus, Lange, Rupprecht, Lehmann, Frank Serge, Macpherson, Andrew, Maerten, Philippe, Maillard, Michel H., Manser, Christine, Manz, Michael, Marbet, Urs, Marx, George, Matter, Christoph, Meier, Rémy, Mendanova, Martina, Michetti, Pierre, Misselwitz, Benjamin, Morell, Bernhard, Mosler, Patrick, Mottet, Christian, Müller, Christoph, Müller, Pascal, Müllhaupt, Beat, Münger-Beyeler, Claudia, Musso, Leilla, Nagy, Andreas, Neagu, Michaela, Nichita, Cristina, Niess, Jan, Nydegger, Andreas, Obialo, Nicole, Oneta, Carl, Oropesa, Cassandra, Peter, Ueli, Peternac, Daniel, Petit, Laetitia Marie, Piccoli-Gfeller, Franziska, Pilz, Julia Beatrice, Pittet, Valérie, Raschle, Nadia, Rentsch, Ronald, Restellini, Sophie, Richterich, Jean-Pierre, Rihs, Sylvia, Ritz, Marc Alain, Roduit, Jocelyn, Rogler, Daniela, Rogler, Gerhard, Rossel, Jean-Benoît, Rueger, Vanessa, Saner, Gaby, Sauter, Bernhard, Sawatzki, Mikael, Schäppi, Michela, Scharl, Michael, Scharl, Sylvie, Schelling, Martin, Schibli, Susanne, Schlauri, Hugo, Uebelhart, Sybille Schmid, Schnegg, Jean-François, Schoepfer, Alain, Seibold, Frank, Seirafi, Mariam, Semadeni, Gian-Marco, Semela, David, Senning, Arne, Sidler, Marc, Sokollik, Christiane, Spalinger, Johannes, Spangenberger, Holger, Stadler, Philippe, Steuerwald, Michael, Straumann, Alex, Straumann-Funk, Bigna, Sulz, Michael, Suter, Alexandra, Thorens, Joël, Tiedemann, Sarah, Tutuian, Radu, Vavricka, Stephan, Viani, Francesco, Vögtlin, Jürg, Von Känel, Roland, Vonlaufen, Alain, Vouillamoz, Dominique, Vulliamy, Rachel, Wermuth, Jürg, Werner, Helene, Wiesel, Paul, Wiest, Reiner, Wylie, Tina, Zeitz, Jonas, Zimmermann, Dorothee, Pittet, Valérie E.H., and Simonson, Thomas

Published
2019
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27. OptoPI3K, genetic code expansion, and click chemistry reveal mechanisms underlying reciprocal regulation between TRPV1 and PI3K

Author

Koh, Duk-Su, primary, Stratiievska, Anastasiia, primary, Jana, Subhashis, additional, Otto, Shauna C., additional, Swanson, Teresa M., additional, Nhim, Anthony, additional, Carlson, Sara, additional, Raza, Marium, additional, Naves, Lígia Araujo, additional, Senning, Eric N., additional, Mehl, Ryan, additional, and Gordon, Sharona E., additional

Published
2023
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30. Monascus sanguineus May Be a Natural Nothospecies

Author

Yatao He, Junlin Liu, Qian Chen, Senning Gan, Ting Sun, and Shengdong Huo

Subjects
Monascus sanguineus, phylogeny, morphology, nothospecies, fungi, natural pigment, Microbiology, QR1-502
Abstract

The genus Monascus has important economic and ecological values. In 2016, we isolated a strain M. sanguineus. After studying the phylogenetic relationship of Monascus, we believe that M. sanguineus is an independent species and speculate that it is a natural nothospecies. Recently, the morphological characteristics and sequences of seven genes (ITS, LSU, β-tubulin, calmodulin, RNA polymerase II subunit, β-ketoacyl synthase, and mating-type locus 1-1) of 15 Monascus strains were analyzed, including sequencing of multiple clones of five protein genes in four M. sanguineus strains. Two types of haplotypes (A and B) were observed in the five protein genes of M. sanguineus. Haplotype A was closely related to M. ruber, and haplotype B may be derived from an unknown Monascus species. The results demonstrated that M. sanguineus including type strains may be a natural nothospecies. This study laid the foundation for further exploration of the M. sanguineus genome, and the study may be of significant importance for the Monascus fermentation industry.

Published
2020
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31. Open eyes and closed eyes elicit different temporal properties of brain functional networks

Author

Yihe Weng, Xiaojin Liu, Huiqing Hu, Huiyuan Huang, Senning Zheng, Qinyuan Chen, Jie Song, Bolin Cao, Junjing Wang, Shuai Wang, and Ruiwang Huang

Subjects
Resting-state fMRI, Eyes condition, Dynamic functional connectivity, k-means, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

The eyes are our windows to the brain. There are differences in brain activity between people who have their eyes closed (EC) and eyes open (EO). Previous studies focused on differences in brain functional properties between these eyes conditions based on an assumption that brain activity is a static phenomenon. However, the dynamic nature of the brain activity in different eyes conditions is still unclear. In this study, we collected resting-state fMRI data from 21 healthy subjects in the EC and EO conditions. Using a sliding time window approach and a k-means clustering algorithm, we calculated the temporal properties of dynamic functional connectivity (dFC) states in the eyes conditions. We also used graph theory to estimate the dynamic topological properties of functional networks in the two conditions. We detected two dFC states, a hyper-connected State 1 and a hypo-connected State 2. We showed the following results: (i) subjects in the EC condition stayed longer in the hyper-connected State 1 than those in the EO; (ii) subjects in the EO condition stayed longer in the hypo-connected State 2 than those in the EC; and (iii) the dFC state transformed into the other state more frequently during EC than during EO. We also found the variance of the characteristic path length was higher during EC than during EO in the hyper-connected State 1. These results indicate that brain activity may be more active and unstable during EC than during EO. Our findings may provide insights into the dynamic nature of the resting-state brain and could be a useful reference for future rs-fMRI studies.

Published
2020
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32. A Study on the Confluence of Resilience Skill Building and Contact Improvisation on Collegiate Dancers

Author

Senning, Connor Bryce

Subjects
Dance, Art education, Performing arts education, Contact, Dance, Improvisation, Resilience, Somatics
Abstract

ABSTRACT OF THESISA Study on the Confluence of Resilience Skill Building andContact Improvisation on Collegiate DancersBY:Connor B. SenningMaster of Fine Arts in DanceUniversity of California, Irvine 2020Dr. Kelli Sharp, Chair This thesis examines five resilience-building skills and their application towards contact improvisation (CI). CI draws upon a mind/body connection while two or more dancers interact spontaneously to effortlessly execute momentum-based partnering. The resilience related skills were applied during three workshops in Fall of 2019 working with ten undergraduate participants. The methodology for this study was qualitative and quantitative to include three main components: literature review, workshops and surveys. Research was conducted by reading printed and electronic texts, as well as by observing CI related documentaries, teachings and performances.The five resilience components researched were self-awareness, self-regulation, mental agility, connection and optimism. In preparation for a professional dance career, participants were asked if the components were useful when applied through the utility of contact improvisation to enhance resiliency. The participants provided responses through surveys as well as verbal feedback to the researcher. The results reveal that resilience practice (through the medium of CI) is practical to an undergraduate community of dancers as well as effective within an undergraduate curriculum. In addition, this multimodal research has informed elements of the students integration with CI as a resilience aid while creating a foundation for myself as an educator and choreographer.

Published
2020

43. Symptoms of Depression and Anxiety Are Independently Associated With Clinical Recurrence of Inflammatory Bowel Disease

Author

Anderegg, Claudia, Bauerfeind, Peter, Beglinger, Christoph, Begré, Stefan, Belli, Dominique, Bengoa, José M., Biedermann, Luc, Bigler, Beat, Binek, Janek, Blattmann, Mirjam, Boehm, Stephan, Borovicka, Jan, Braegger, Christian P., Brunner, Nora, Bühr, Patrick, Burnand, Bernard, Burri, Emanuel, Buyse, Sophie, Cremer, Matthias, Criblez, Dominique H., de Saussure, Philippe, Degen, Lukas, Delarive, Joakim, Doerig, Christopher, Dora, Barbara, Dorta, Gian, Egger, Mara, Ehmann, Tobias, El-Wafa, Ali, Engelmann, Matthias, Ezri, Jessica, Felley, Christian, Fliegner, Markus, Fournier, Nicolas, Fraga, Montserrat, Frei, Pascal, Frei, Remus, Fried, Michael, Froehlich, Florian, Funk, Christian, Ivano Furlano, Raoul, Gallot-Lavallée, Suzanne, Geyer, Martin, Girardin, Marc, Golay, Delphine, Grandinetti, Tanja, Gysi, Beat, Haack, Horst, Haarer, Johannes, Helbling, Beat, Hengstler, Peter, Herzog, Denise, Hess, Cyrill, Heyland, Klaas, Hinterleitner, Thomas, Hiroz, Philippe, Hirschi, Claudia, Hruz, Petr, Iwata, Rika, Jost, Res, Juillerat, Pascal, Kessler Brondolo, Vera, Knellwolf, Christina, Knoblauch, Christoph, Köhler, Henrik, Koller, Rebekka, Krieger-Grübel, Claudia, Kullak-Ublick, Gerd, Künzler, Patrizia, Landolt, Markus, Lange, Rupprecht, Serge Lehmann, Frank, Macpherson, Andrew, Maerten, Philippe, Maillard, Michel H., Manser, Christine, Manz, Michael, Marbet, Urs, Marx, George, Matter, Christoph, McLin, Valérie, Meier, Rémy, Mendanova, Martina, Meyenberger, Christa, Michetti, Pierre, Misselwitz, Benjamin, Moradpour, Darius, Morell, Bernhard, Mosler, Patrick, Mottet, Christian, Müller, Christoph, Müller, Pascal, Müllhaupt, Beat, Münger-Beyeler, Claudia, Musso, Leilla, Nagy, Andreas, Neagu, Michaela, Nichita, Cristina, Niess, Jan, Noël, Natacha, Nydegger, Andreas, Obialo, Nicole, Oneta, Carl, Oropesa, Cassandra, Peter, Ueli, Peternac, Daniel, Marie Petit, Laetitia, Piccoli-Gfeller, Franziska, Beatrice Pilz, Julia, Pittet, Valérie, Raschle, Nadia, Rentsch, Ronald, Restellini, Sophie, Richterich, Jean-Pierre, Rihs, Sylvia, Alain Ritz, Marc, Roduit, Jocelyn, Rogler, Daniela, Rogler, Gerhard, Rossel, Jean-Benoît, Sagmeister, Markus, Saner, Gaby, Sauter, Bernhard, Sawatzki, Mikael, Schäppi, Michela, Scharl, Michael, Schelling, Martin, Schibli, Susanne, Schlauri, Hugo, Schmid Uebelhart, Sybille, Schnegg, Jean-François, Schoepfer, Alain, Seibold, Frank, Seirafi, Mariam, Semadeni, Gian-Marco, Semela, David, Senning, Arne, Sidler, Marc, Sokollik, Christiane, Spalinger, Johannes, Spangenberger, Holger, Stadler, Philippe, Steuerwald, Michael, Straumann, Alex, Straumann-Funk, Bigna, Sulz, Michael, Thorens, Joël, Tiedemann, Sarah, Tutuian, Radu, Vavricka, Stephan, Viani, Francesco, Vögtlin, Jürg, Von Känel, Roland, Vonlaufen, Alain, Vouillamoz, Dominique, Vulliamy, Rachel, Wermuth, Jürg, Werner, Helene, Wiesel, Paul, Wiest, Reiner, Wylie, Tina, Zeitz, Jonas, Zimmermann, Dorothee, Mikocka-Walus, Antonina, Pittet, Valerie, and von Känel, Roland

Published
2016
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44. Reciprocal regulation among TRPV1 channels and phosphoinositide 3-kinase in response to nerve growth factor

Author

Anastasiia Stratiievska, Sara Nelson, Eric N Senning, Jonathan D Lautz, Stephen EP Smith, and Sharona E Gordon

Subjects
TRPV1, NGF, PI3K, inflammation, PIP3, TRPV2, Medicine, Science, Biology (General), QH301-705.5
Abstract

Although it has been known for over a decade that the inflammatory mediator NGF sensitizes pain-receptor neurons through increased trafficking of TRPV1 channels to the plasma membrane, the mechanism by which this occurs remains mysterious. NGF activates phosphoinositide 3-kinase (PI3K), the enzyme that generates PI(3,4)P2 and PIP3, and PI3K activity is required for sensitization. One tantalizing hint came from the finding that the N-terminal region of TRPV1 interacts directly with PI3K. Using two-color total internal reflection fluorescence microscopy, we show that TRPV1 potentiates NGF-induced PI3K activity. A soluble TRPV1 fragment corresponding to the N-terminal Ankyrin repeats domain (ARD) was sufficient to produce this potentiation, indicating that allosteric regulation was involved. Further, other TRPV channels with conserved ARDs also potentiated NGF-induced PI3K activity. Our data demonstrate a novel reciprocal regulation of PI3K signaling by the ARD of TRPV channels.

Published
2018
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