10 results on '"Enrique Navas-Perez"'
Search Results
2. Metazoan evolution of glutamate receptors reveals unreported phylogenetic groups and divergent lineage-specific events
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David Ramos-Vicente, Jie Ji, Esther Gratacòs-Batlle, Gemma Gou, Rita Reig-Viader, Javier Luís, Demian Burguera, Enrique Navas-Perez, Jordi García-Fernández, Pablo Fuentes-Prior, Hector Escriva, Nerea Roher, David Soto, and Àlex Bayés
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phylogenetics ,ionotropic glutamate receptors ,metabotropic glutamate receptors ,electrophysiology ,gene expression ,amphioxus ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Glutamate receptors are divided in two unrelated families: ionotropic (iGluR), driving synaptic transmission, and metabotropic (mGluR), which modulate synaptic strength. The present classification of GluRs is based on vertebrate proteins and has remained unchanged for over two decades. Here we report an exhaustive phylogenetic study of GluRs in metazoans. Importantly, we demonstrate that GluRs have followed different evolutionary histories in separated animal lineages. Our analysis reveals that the present organization of iGluRs into six classes does not capture the full complexity of their evolution. Instead, we propose an organization into four subfamilies and ten classes, four of which have never been previously described. Furthermore, we report a sister class to mGluR classes I-III, class IV. We show that many unreported proteins are expressed in the nervous system, and that new Epsilon receptors form functional ligand-gated ion channels. We propose an updated classification of glutamate receptors that includes our findings.
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- 2018
- Full Text
- View/download PDF
3. Characterization of an eutherian gene cluster generated after transposon domestication identifies Bex3 as relevant for advanced neurological functions
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Pol Cuscó, Demian Burguera, Salvatore D'Aniello, Cristina Vicente-García, Bru Cormand, Enrique Navas-Perez, José Luis Ferran, Jordi Garcia-Fernàndez, Carlos Herrera-Úbeda, Marta Alaiz-Noya, Rafael Falcón-Moya, Angel M. Carrión, Serena Mirra, Irene Suárez-Pereira, Gemma Marfany, Fausto Ulloa, Eduardo Soriano, Noèlia Fernàndez-Castillo, Ester Antón-Galindo, Jaime J. Carvajal, Antonio Rodríguez-Moreno, Macarena López-Mayorga, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Junta de Andalucía, Centro de Investigación Biomédica en Red Enfermedades Raras (España), [Navas-Pérez,E, Mirra,S, Burguera,D, Fernàndez-Castillo,N, Antón-Galindo,E, Herrera-Úbeda,C, Cormand,B, Marfany,G, Garcia-Fernàndez,J] Department of Genetics, Microbiology and Statistics, Faculty of Biology, and Institut de Biomedicina (IBUB), University of Barcelona, Barcelona, Spain. [Vicente-García,C, López-Mayorga,M, Carvajal,JJ] Centro Andaluz de Biología del Desarrollo, CSIC-UPO-JA, Universidad Pablo de Olavide, Sevilla, Spain. [Mirra,S, Ulloa,F, Soriano,E] Department of Cell Biology, Physiology and Immunology, and Institute of Neurosciences, University of Barcelona, Barcelona, Spain. [Mirra,S, Marfany,G] Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Mirra,S, Soriano,E] Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Burguera,D] Department of Zoology, Charles University, Prague, Czech Republic. [Fernàndez-Castillo,N, Marfany,G] Institut de Recerca Sant Joan de Déu (IR-SJD), Esplugues de Llobregat, Barcelona, Spain. [Ferrán,JL] Department of Human Anatomy, School of Medicine, University of Murcia and IMIB-Arrixaca Institute, Murcia, Spain. [Alaiz-Noya,M, Suárez-Pereira,I, Falcón-Moya,R, Rodríguez-Moreno,A, Carrión,AM] Department of Physiology, Anatomy and Cell Biology, Universidad Pablo de Olavide, Sevilla, Spain. [Alaiz-Noya,M] Present Address: Instituto de Neurociencias de Alicante (Universidad Miguel Hernández - Consejo Superior de Investigaciones Científicas), Alicante, Spain. [Suárez-Pereira,I] Present Address: Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Neuropsychopharmacology and psychobiology research group, UCA, INiBICA, Cádiz, Spain. [Cuscó,P] Genome Architecture, Gene Regulation, Stem Cells and Cancer Programme, Centre for Genomic Regulation (CRG), the Barcelona Institute of Science and Technology, Barcelona, Spain. [Cuscó,P] Universitat Pompeu Fabra (UPF), Barcelona, Spain. [D'Aniello,S] Department of Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn, Naples, Italy. [Soriano,E] Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain., and Major financial support for this research was received from Spanish 'Ministerio de Ciencia, Innovación y Universidades.' Grants BFU2015-68655-P and BFU2017-861152-P to J.G.F., RTI2018-100968-B-I00, 2017-SGR-738, H2020/2014-2020 under grant agreements n°667302, n°643051, and n°728018 to B.C., PGC2018-098229-B-I00 to J.L.F., BES-2016-077374 to E.A.-G., CVI-7290 Junta de Andalucía to A.R.M., SAF2016-80937-R (Ministerio de Economía y Competitividad/FEDER) to G.M., Institutional Grant MDM-2016-0687 (Maria de Maeztu Excellence Unit, Department of Gene Regulation and Morphogenesis at CABD) and BFU2017-83150-P to J.J.C, BFU2017-89780-R and P12-CTS-2257 to A.M.C. and SAF2016-76340-R and María de Maeztu Excellence Unit, Institute of Neurosciences to E.S.. E.N.P. held an FPI pre-doctoral fellowship (Spanish 'Ministerio de Ciencia, Innovación y Universidades'). S.M. was first supported by a contract with the 'Centro de Investigación Biomédica en Enfermedades Neurodegenerativas,' and later by 'Centro de Investigación Biomédica en Red de Enfermedades Raras' (CIBERER). N.F.C. is also under contract by CIBERER. This study makes use of data generated by the DECIPHER community. A full list of centres who contributed to the generation of the data is available at http://decipher.sanger.ac.uk and via email from decipher@sanger.ac.uk. Funding for the project was provided by the Wellcome Trust.
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Bex3 ,Tceal ,Placenta ,Autism ,Genome ,Neurodevelopmental disorders ,Familia de multigenes ,Domestication ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Mice ,0302 clinical medicine ,Human genetics ,Pregnancy ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Nerve Tissue Proteins [Medical Subject Headings] ,Gene duplication ,Gene cluster ,Organisms::Eukaryota::Animals [Medical Subject Headings] ,Autism spectrum disorder ,Genetic novelty ,lcsh:QH301-705.5 ,Serina-treonina quinasas TOR ,Phylogeny ,Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Reproductive Physiological Processes::Reproduction::Pregnancy [Medical Subject Headings] ,Mice, Knockout ,0303 health sciences ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Nuclear Proteins [Medical Subject Headings] ,Genètica humana ,Eutheria ,TOR Serine-Threonine Kinases ,Brain ,Nuclear Proteins ,DNA-Binding Proteins ,Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Genetically Modified::Mice, Transgenic::Mice, Knockout [Medical Subject Headings] ,Multigene Family ,Placental mammals ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins [Medical Subject Headings] ,mTOR ,Female ,Transposon domestication ,Transposable element ,lcsh:QH426-470 ,Psychiatry and Psychology::Mental Disorders::Mental Disorders Diagnosed in Childhood::Child Development Disorders, Pervasive::Autistic Disorder [Medical Subject Headings] ,Nerve Tissue Proteins ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Intracellular Signaling Peptides and Proteins::Apoptosis Regulatory Proteins [Medical Subject Headings] ,Biology ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors [Medical Subject Headings] ,Evolution, Molecular ,03 medical and health sciences ,Trastornos del neurodesarrollo ,Animals ,Humans ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Intracellular Signaling Peptides and Proteins::TOR Serine-Threonine Kinases [Medical Subject Headings] ,Allele ,Gene ,030304 developmental biology ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings] ,Research ,Anatomy::Nervous System::Central Nervous System::Brain [Medical Subject Headings] ,Anatomy::Embryonic Structures::Placenta [Medical Subject Headings] ,Phenomena and Processes::Biological Phenomena::Biological Processes::Biological Evolution::Evolution, Molecular [Medical Subject Headings] ,Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epigenesis, Genetic::Gene Silencing::CRISPR-Cas Systems [Medical Subject Headings] ,Mice, Inbred C57BL ,lcsh:Genetics ,Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Interspersed Repetitive Sequences::DNA Transposable Elements [Medical Subject Headings] ,lcsh:Biology (General) ,Check Tags::Female [Medical Subject Headings] ,Evolutionary biology ,DNA Transposable Elements ,Euterios ,Phenomena and Processes::Genetic Phenomena::Phylogeny [Medical Subject Headings] ,Trastorno del espectro autista ,CRISPR-Cas Systems ,Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Laboratory::Animals, Inbred Strains::Mice, Inbred Strains::Mice, Inbred C57BL [Medical Subject Headings] ,Autisme ,Apoptosis Regulatory Proteins ,Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Multigene Family [Medical Subject Headings] ,030217 neurology & neurosurgery ,Transcription Factors - Abstract
[Background]: One of the most unusual sources of phylogenetically restricted genes is the molecular domestication of transposable elements into a host genome as functional genes. Although these kinds of events are sometimes at the core of key macroevolutionary changes, their origin and organismal function are generally poorly understood., [Results]: Here, we identify several previously unreported transposable element domestication events in the human and mouse genomes. Among them, we find a remarkable molecular domestication that gave rise to a multigenic family in placental mammals, the Bex/Tceal gene cluster. These genes, which act as hub proteins within diverse signaling pathways, have been associated with neurological features of human patients carrying genomic microdeletions in chromosome X. The Bex/Tceal genes display neural-enriched patterns and are differentially expressed in human neurological disorders, such as autism and schizophrenia. Two different murine alleles of the cluster member Bex3 display morphological and physiopathological brain modifications, such as reduced interneuron number and hippocampal electrophysiological imbalance, alterations that translate into distinct behavioral phenotypes., [Conclusions]: We provide an in-depth understanding of the emergence of a gene cluster that originated by transposon domestication and gene duplication at the origin of placental mammals, an evolutionary process that transformed a non-functional transposon sequence into novel components of the eutherian genome. These genes were integrated into existing signaling pathways involved in the development, maintenance, and function of the CNS in eutherians. At least one of its members, Bex3, is relevant for higher brain functions in placental mammals and may be involved in human neurological disorders., Major financial support for this research was received from Spanish “Ministerio de Ciencia, Innovación y Universidades.” Grants BFU2015-68655-P and BFU2017-861152-P to J.G.F., RTI2018-100968-B-I00, 2017-SGR-738, H2020/2014-2020 under grant agreements n°667302, n°643051, and n°728018 to B.C., PGC2018-098229-B-I00 to J.L.F., BES-2016-077374 to E.A.-G., CVI-7290 Junta de Andalucía to A.R.M., SAF2016-80937-R (Ministerio de Economía y Competitividad/FEDER) to G.M., Institutional Grant MDM-2016-0687 (Maria de Maeztu Excellence Unit, Department of Gene Regulation and Morphogenesis at CABD) and BFU2017-83150-P to J.J.C, BFU2017-89780-R and P12-CTS-2257 to A.M.C. and SAF2016-76340-R and María de Maeztu Excellence Unit, Institute of Neurosciences to E.S.. E.N.P. held an FPI pre-doctoral fellowship (Spanish “Ministerio de Ciencia, Innovación y Universidades”). S.M. was first supported by a contract with the “Centro de Investigación Biomédica en Enfermedades Neurodegenerativas,” and later by “Centro de Investigación Biomédica en Red de Enfermedades Raras” (CIBERER). N.F.C. is also under contract by CIBERER.
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- 2020
4. Microsyntenic Clusters Reveal Conservation of lncRNAs in Chordates Despite Absence of Sequence Conservation
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Marta Marin-Barba, Jordi Garcia-Fernàndez, Beatriz Albuixech-Crespo, Grant N. Wheeler, Jan Gravemeyer, Carlos Herrera-Úbeda, and Enrique Navas-Perez
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0301 basic medicine ,animal structures ,Xenopus ,lncRNAs ,Cordats ,Biology ,amphioxus ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Intergenic region ,Chordata ,Gene ,lcsh:QH301-705.5 ,Synteny ,Sequence (medicine) ,genome_evolution ,General Immunology and Microbiology ,synteny ,Genomics ,biology.organism_classification ,Phenotype ,Genòmica ,030104 developmental biology ,lcsh:Biology (General) ,Evolutionary biology ,Human genome ,General Agricultural and Biological Sciences ,030217 neurology & neurosurgery ,Function (biology) - Abstract
Homologous long non-coding RNAs (lncRNAs) are elusive to identify by sequence similarity due to their fast-evolutionary rate. Here we develop LincOFinder, a pipeline that finds conserved intergenic lncRNAs (lincRNAs) between distant related species by means of microsynteny analyses. Using this tool, we have identified 16 bona fide homologous lincRNAs between the amphioxus and human genomes. We characterized and compared in amphioxus and Xenopus the expression domain of one of them, Hotairm1, located in the anterior part of the Hox cluster. In addition, we analyzed the function of this lincRNA in Xenopus, showing that its disruption produces a severe headless phenotype, most probably by interfering with the regulation of the Hox cluster. Our results strongly suggest that this lincRNA has probably been regulating the Hox cluster since the early origin of chordates. Our work pioneers the use of syntenic searches to identify non-coding genes over long evolutionary distances and helps to further understand lncRNA evolution.
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- 2019
5. Author response: Metazoan evolution of glutamate receptors reveals unreported phylogenetic groups and divergent lineage-specific events
- Author
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Hector Escriva, Demian Burguera, Esther Gratacòs-Batlle, Jie Ji, Nerea Roher, Rita Reig-Viader, David Ramos-Vicente, Pablo Fuentes-Prior, Àlex Bayés, Gemma Gou, Jordi Garcia-Fernàndez, Enrique Navas-Perez, David Soto, and Javier Luís
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Lineage specific ,Phylogenetic tree ,Evolutionary biology ,Glutamate receptor ,Biology - Published
- 2018
6. Characterization of an eutherian gene cluster generated after transposon domestication identifies Bex3 as relevant for advanced neurological functions
- Author
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Enrique Navas-Pérez, Cristina Vicente-García, Serena Mirra, Demian Burguera, Noèlia Fernàndez-Castillo, José Luis Ferrán, Macarena López-Mayorga, Marta Alaiz-Noya, Irene Suárez-Pereira, Ester Antón-Galindo, Fausto Ulloa, Carlos Herrera-Úbeda, Pol Cuscó, Rafael Falcón-Moya, Antonio Rodríguez-Moreno, Salvatore D’Aniello, Bru Cormand, Gemma Marfany, Eduardo Soriano, Ángel M. Carrión, Jaime J. Carvajal, and Jordi Garcia-Fernàndez
- Subjects
Genetic novelty ,Transposon domestication ,Bex3 ,Tceal ,Placental mammals ,Gene cluster ,Biology (General) ,QH301-705.5 ,Genetics ,QH426-470 - Abstract
Abstract Background One of the most unusual sources of phylogenetically restricted genes is the molecular domestication of transposable elements into a host genome as functional genes. Although these kinds of events are sometimes at the core of key macroevolutionary changes, their origin and organismal function are generally poorly understood. Results Here, we identify several previously unreported transposable element domestication events in the human and mouse genomes. Among them, we find a remarkable molecular domestication that gave rise to a multigenic family in placental mammals, the Bex/Tceal gene cluster. These genes, which act as hub proteins within diverse signaling pathways, have been associated with neurological features of human patients carrying genomic microdeletions in chromosome X. The Bex/Tceal genes display neural-enriched patterns and are differentially expressed in human neurological disorders, such as autism and schizophrenia. Two different murine alleles of the cluster member Bex3 display morphological and physiopathological brain modifications, such as reduced interneuron number and hippocampal electrophysiological imbalance, alterations that translate into distinct behavioral phenotypes. Conclusions We provide an in-depth understanding of the emergence of a gene cluster that originated by transposon domestication and gene duplication at the origin of placental mammals, an evolutionary process that transformed a non-functional transposon sequence into novel components of the eutherian genome. These genes were integrated into existing signaling pathways involved in the development, maintenance, and function of the CNS in eutherians. At least one of its members, Bex3, is relevant for higher brain functions in placental mammals and may be involved in human neurological disorders.
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- 2020
- Full Text
- View/download PDF
7. Characterization of the TLR Family in Branchiostoma lanceolatum and Discovery of a Novel TLR22-Like Involved in dsRNA Recognition in Amphioxus
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Jie Ji, David Ramos-Vicente, Enrique Navas-Pérez, Carlos Herrera-Úbeda, José Miguel Lizcano, Jordi Garcia-Fernàndez, Hector Escrivà, Àlex Bayés, and Nerea Roher
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toll-like receptor ,TLR ,evolution ,amphioxus ,Poly I:C ,TLR22 ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Toll-like receptors (TLRs) are important for raising innate immune responses in both invertebrates and vertebrates. Amphioxus belongs to an ancient chordate lineage which shares key features with vertebrates. The genomic research on TLR genes in Branchiostoma floridae and Branchiostoma belcheri reveals the expansion of TLRs in amphioxus. However, the repertoire of TLRs in Branchiostoma lanceolatum has not been studied and the functionality of amphioxus TLRs has not been reported. We have identified from transcriptomic data 30 new putative TLRs in B. lanceolatum and all of them are transcribed in adult amphioxus. Phylogenetic analysis showed that the repertoire of TLRs consists of both non-vertebrate and vertebrate-like TLRs. It also indicated a lineage-specific expansion in orthologous clusters of the vertebrate TLR11 family. We did not detect any representatives of the vertebrate TLR1, TLR3, TLR4, TLR5 and TLR7 families. To gain insight into these TLRs, we studied in depth a particular TLR highly similar to a B. belcheri gene annotated as bbtTLR1. The phylogenetic analysis of this novel BlTLR showed that it clusters with the vertebrate TLR11 family and it might be more related to TLR13 subfamily according to similar domain architecture. Transient and stable expression in HEK293 cells showed that the BlTLR localizes on the plasma membrane, but it did not respond to the most common mammalian TLR ligands. However, when the ectodomain of BlTLR is fused to the TIR domain of human TLR2, the chimeric protein could indeed induce NF-κB transactivation in response to the viral ligand Poly I:C, also indicating that in amphioxus, specific accessory proteins are needed for downstream activation. Based on the phylogenetic, subcellular localization and functional analysis, we propose that the novel BlTLR might be classified as an antiviral receptor sharing at least partly the functions performed by vertebrate TLR22. TLR22 is thought to be viral teleost-specific TLR but here we demonstrate that teleosts and amphioxus TLR22-like probably shared a common ancestor. Additional functional studies with other lancelet TLR genes will enrich our understanding of the immune response in amphioxus and will provide a unique perspective on the evolution of the immune system.
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- 2018
- Full Text
- View/download PDF
8. Microsyntenic Clusters Reveal Conservation of lncRNAs in Chordates Despite Absence of Sequence Conservation
- Author
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Carlos Herrera-Úbeda, Marta Marín-Barba, Enrique Navas-Pérez, Jan Gravemeyer, Beatriz Albuixech-Crespo, Grant N. Wheeler, and Jordi Garcia-Fernàndez
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lncRNAs ,genome_evolution ,synteny ,amphioxus ,Biology (General) ,QH301-705.5 - Abstract
Homologous long non-coding RNAs (lncRNAs) are elusive to identify by sequence similarity due to their fast-evolutionary rate. Here we develop LincOFinder, a pipeline that finds conserved intergenic lncRNAs (lincRNAs) between distant related species by means of microsynteny analyses. Using this tool, we have identified 16 bona fide homologous lincRNAs between the amphioxus and human genomes. We characterized and compared in amphioxus and Xenopus the expression domain of one of them, Hotairm1, located in the anterior part of the Hox cluster. In addition, we analyzed the function of this lincRNA in Xenopus, showing that its disruption produces a severe headless phenotype, most probably by interfering with the regulation of the Hox cluster. Our results strongly suggest that this lincRNA has probably been regulating the Hox cluster since the early origin of chordates. Our work pioneers the use of syntenic searches to identify non-coding genes over long evolutionary distances and helps to further understand lncRNA evolution.
- Published
- 2019
- Full Text
- View/download PDF
9. The Armc10/SVH gene: Genome context, regulation of mitochondrial dynamics and protection against Aβ-induced mitochondrial fragmentation
- Author
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Joana Figueiro-Silva, Guillermo López-Doménech, Jordi Garcia-Fernàndez, Martí Quevedo, Roman Serrat, Enrique Navas-Perez, Eduardo Soriano, Ramon Trullas, Petar Podlesniy, Fausto Ulloa, Serena Mirra, Universitat de Barcelona, Ministerio de Economía y Competitividad (España), Generalitat de Catalunya, and Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España)
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Cancer Research ,Molecular Sequence Data ,Immunology ,Kinesins ,Neurones ,Mitochondrion ,Biology ,MT-RNR1 ,Hippocampus ,Synteny ,Mitocondris ,Mice ,Cellular and Molecular Neuroscience ,Gene cluster ,Membrane proteins ,Animals ,Humans ,Protein Isoforms ,Gene family ,Amino Acid Sequence ,Conserved Sequence ,HSPA9 ,Armadillo Domain Proteins ,Aβ-toxicity ,Genetics ,Neurons ,Amyloid beta-Peptides ,Genome ,Mitochondrial fission ,Mitophagy ,Proteïnes de membrana ,Cell Biology ,Expressió gènica ,Axons ,Mitochondria ,HEK293 Cells ,mitochondrial fusion ,Cytoprotection ,Genetic Loci ,DNAJA3 ,Mitochondrial dynamics ,Original Article ,Gene expression ,Ab-toxicity ,Protein Binding - Abstract
Mitochondrial function and dynamics are essential for neurotransmission, neural function and neuronal viability. Recently, we showed that the eutherian-specific Armcx gene cluster (Armcx1-6 genes), located in the X chromosome, encodes for a new family of proteins that localise to mitochondria, regulating mitochondrial trafficking. The Armcx gene cluster evolved by retrotransposition of the Armc10 gene mRNA, which is present in all vertebrates and is considered to be the ancestor gene. Here we investigate the genomic organisation, mitochondrial functions and putative neuroprotective role of the Armc10 ancestor gene. The genomic context of the Armc10 locus shows considerable syntenic conservation among vertebrates, and sequence comparisons and CHIP-data suggest the presence of at least three conserved enhancers. We also show that the Armc10 protein localises to mitochondria and that it is highly expressed in the brain. Furthermore, we show that Armc10 levels regulate mitochondrial trafficking in neurons, but not mitochondrial aggregation, by controlling the number of moving mitochondria. We further demonstrate that the Armc10 protein interacts with the KIF5/Miro1-2/Trak2 trafficking complex. Finally, we show that overexpression of Armc10 in neurons prevents Aß-induced mitochondrial fission and neuronal death. Our data suggest both conserved and differential roles of the Armc10/Armcx gene family in regulating mitochondrial dynamics in neurons, and underscore a protective effect of the Armc10 gene against Aß-induced toxicity. Overall, our findings support a further degree of regulation of mitochondrial dynamics in the brain of more evolved mammals. © 2014 Macmillan Publishers Limited All rights reserved., This project was supported by grants BFU2008-3980 and SAF2011-13232-E (Acciones Complementarias) (MINECO, Spain) to ES, by grant BFU2010-21507 to FU, by grant SAF2011-23550 to RT, by grant ‘BFU2011-23921’ and the ICREA Academia Prize (Generalitat de Catalunya) to JGF, and by a grant from the CIBERNED. SM and EN hold FPI fellowships
10. Evolutionary recruitment of flexible Esrp-dependent splicing programs into diverse embryonic morphogenetic processes
- Author
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Claudia Cuomo, Ylenia D’Agostino, Claudia Racioppi, Ana Riesgo, Rosaria Esposito, Lucia Fanlo, Yamile Marquez, Giovanna Benvenuto, Filomena Ristoratore, Salvatore D'Aniello, Enrique Navas-Perez, Jon Permanyer, Jordi Garcia-Fernàndez, Manuel Irimia, Andre Gohr, Antonio Torres-Méndez, Demian Burguera, Elisa Martí, Lionel Christiaen, Maria Ina Arnone, Beatriz Albuixech-Crespo, Antonietta Spagnuolo, Universitat de Barcelona, European Research Council, Ministerio de Economía y Competitividad (España), Institución Catalana de Investigación y Estudios Avanzados, Generalitat de Catalunya, Universidad de Barcelona, EMBO, Garcia-Fernàndez, Jordi [0000-0001-5677-5970], Benvenuto, Giovanna [0000-0001-7155-2935], Torres-Mendéz, Antonio [0000-0002-1241-8629], Christiaen, Lionel A. [0000-0001-5930-5667], Ristoratore, Filomena [0000-0002-6023-9537], Irimia, Manuel [0000-0002-2179-2567], Garcia-Fernàndez, Jordi, Benvenuto, Giovanna, Torres-Mendéz, Antonio, Christiaen, Lionel A., Ristoratore, Filomena, and Irimia, Manuel
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0301 basic medicine ,Male ,Embryology ,General Physics and Astronomy ,Sequence Homology ,Ectoderm ,Esrp genes ,Morphogenesis ,Developmental ,Molecular genetics ,Animal Structures ,lcsh:Science ,Zebrafish ,Lancelets ,Multidisciplinary ,Deuterostome ,biology ,Morfogènesi ,Gene Expression Regulation, Developmental ,Vertebrate ,RNA-Binding Proteins ,Exons ,Biological Evolution ,Amino Acid ,medicine.anatomical_structure ,Gene Knockdown Techniques ,RNA splicing ,Animals ,CRISPR-Cas Systems ,Embryonic Development ,Epithelial-Mesenchymal Transition ,Female ,Mutation ,RNA Splicing ,Sequence Homology, Amino Acid ,Signal Transduction ,Strongylocentrotus purpuratus ,Urochordata ,Evolutionary developmental biology ,Science ,Organogenesis ,Article ,General Biochemistry, Genetics and Molecular Biology ,Genètica molecular ,03 medical and health sciences ,biology.animal ,Regulació genètica ,medicine ,Transcriptomics ,Genetic regulation ,Embriologia ,General Chemistry ,biology.organism_classification ,Embryonic stem cell ,030104 developmental biology ,Gene Expression Regulation ,Evolutionary biology ,lcsh:Q - Abstract
Epithelial-mesenchymal interactions are crucial for the development of numerous animal structures. Thus, unraveling how molecular tools are recruited in different lineages to control interplays between these tissues is key to understanding morphogenetic evolution. Here, we study Esrp genes, which regulate extensive splicing programs and are essential for mammalian organogenesis. We find that Esrp homologs have been independently recruited for the development of multiple structures across deuterostomes. Although Esrp is involved in a wide variety of ontogenetic processes, our results suggest ancient roles in non-neural ectoderm and regulating specific mesenchymal-to-epithelial transitions in deuterostome ancestors. However, consistent with the extensive rewiring of Esrp-dependent splicing programs between phyla, most developmental defects observed in vertebrate mutants are related to other types of morphogenetic processes. This is likely connected to the origin of an event in Fgfr, which was recruited as an Esrp target in stem chordates and subsequently co-opted into the development of many novel traits in vertebrates., This work has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No ERC-StG-LS2-637591 to M.I.), the Spanish Ministry of Economy and Competitiveness (grant BFU2014-58908P to J.G.-F, BFU2014-55076-P to M.I., and the ‘Centro de Excelencia Severo Ochoa 2013–2017’, SEV-2012-0208), and ICREA - Generalitat de Catalunya (Academia Prize to J.G.-F). We acknowledge the support of the CERCA Programme/Generalitat de Catalunya. D.B. held an APIF fellowship from University of Barcelona, Y.M. an EMBO Long Term postdoctoral fellowship (ALTF 1505-2015), C.R. an EMBO long-term fellowship (ALTF 1608-2014), ATM an FPI-SO fellowship.
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