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Ras and Rab interactor 1 controls neuronal plasticity by coordinating dendritic filopodial motility and AMPA receptor turnover

Ras and Rab interactor 1 (RIN1) is predominantly expressed in the nervous system. RIN1-knockout animals have deficits in latent inhibition and fear extinction in the amygdala, suggesting a critical role for RIN1 in preventing the persistence of unpleasant memories. At the molecular level, RIN1 signa...

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Autores principales: Szíber, Zsófia, Liliom, Hanna, Morales, Carlos O. Oueslati, Ignácz, Attila, Rátkai, Anikó Erika, Ellwanger, Kornelia, Link, Gisela, Szűcs, Attila, Hausser, Angelika, Schlett, Katalin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5231897/
https://www.ncbi.nlm.nih.gov/pubmed/27852895
http://dx.doi.org/10.1091/mbc.E16-07-0526
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author Szíber, Zsófia
Liliom, Hanna
Morales, Carlos O. Oueslati
Ignácz, Attila
Rátkai, Anikó Erika
Ellwanger, Kornelia
Link, Gisela
Szűcs, Attila
Hausser, Angelika
Schlett, Katalin
author_facet Szíber, Zsófia
Liliom, Hanna
Morales, Carlos O. Oueslati
Ignácz, Attila
Rátkai, Anikó Erika
Ellwanger, Kornelia
Link, Gisela
Szűcs, Attila
Hausser, Angelika
Schlett, Katalin
author_sort Szíber, Zsófia
collection PubMed
description Ras and Rab interactor 1 (RIN1) is predominantly expressed in the nervous system. RIN1-knockout animals have deficits in latent inhibition and fear extinction in the amygdala, suggesting a critical role for RIN1 in preventing the persistence of unpleasant memories. At the molecular level, RIN1 signals through Rab5 GTPases that control endocytosis of cell-surface receptors and Abl nonreceptor tyrosine kinases that participate in actin cytoskeleton remodeling. Here we report that RIN1 controls the plasticity of cultured mouse hippocampal neurons. Our results show that RIN1 affects the morphology of dendritic protrusions and accelerates dendritic filopodial motility through an Abl kinase–dependent pathway. Lack of RIN1 results in enhanced mEPSC amplitudes, indicating an increase in surface AMPA receptor levels compared with wild-type neurons. We further provide evidence that the Rab5 GEF activity of RIN1 regulates surface GluA1 subunit endocytosis. Consequently loss of RIN1 blocks surface AMPA receptor down-regulation evoked by chemically induced long-term depression. Our findings indicate that RIN1 destabilizes synaptic connections and is a key player in postsynaptic AMPA receptor endocytosis, providing multiple ways of negatively regulating memory stabilization during neuronal plasticity.
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spelling pubmed-52318972017-03-30 Ras and Rab interactor 1 controls neuronal plasticity by coordinating dendritic filopodial motility and AMPA receptor turnover Szíber, Zsófia Liliom, Hanna Morales, Carlos O. Oueslati Ignácz, Attila Rátkai, Anikó Erika Ellwanger, Kornelia Link, Gisela Szűcs, Attila Hausser, Angelika Schlett, Katalin Mol Biol Cell Articles Ras and Rab interactor 1 (RIN1) is predominantly expressed in the nervous system. RIN1-knockout animals have deficits in latent inhibition and fear extinction in the amygdala, suggesting a critical role for RIN1 in preventing the persistence of unpleasant memories. At the molecular level, RIN1 signals through Rab5 GTPases that control endocytosis of cell-surface receptors and Abl nonreceptor tyrosine kinases that participate in actin cytoskeleton remodeling. Here we report that RIN1 controls the plasticity of cultured mouse hippocampal neurons. Our results show that RIN1 affects the morphology of dendritic protrusions and accelerates dendritic filopodial motility through an Abl kinase–dependent pathway. Lack of RIN1 results in enhanced mEPSC amplitudes, indicating an increase in surface AMPA receptor levels compared with wild-type neurons. We further provide evidence that the Rab5 GEF activity of RIN1 regulates surface GluA1 subunit endocytosis. Consequently loss of RIN1 blocks surface AMPA receptor down-regulation evoked by chemically induced long-term depression. Our findings indicate that RIN1 destabilizes synaptic connections and is a key player in postsynaptic AMPA receptor endocytosis, providing multiple ways of negatively regulating memory stabilization during neuronal plasticity. The American Society for Cell Biology 2017-01-15 /pmc/articles/PMC5231897/ /pubmed/27852895 http://dx.doi.org/10.1091/mbc.E16-07-0526 Text en © 2017 Szíber et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Szíber, Zsófia
Liliom, Hanna
Morales, Carlos O. Oueslati
Ignácz, Attila
Rátkai, Anikó Erika
Ellwanger, Kornelia
Link, Gisela
Szűcs, Attila
Hausser, Angelika
Schlett, Katalin
Ras and Rab interactor 1 controls neuronal plasticity by coordinating dendritic filopodial motility and AMPA receptor turnover
title Ras and Rab interactor 1 controls neuronal plasticity by coordinating dendritic filopodial motility and AMPA receptor turnover
title_full Ras and Rab interactor 1 controls neuronal plasticity by coordinating dendritic filopodial motility and AMPA receptor turnover
title_fullStr Ras and Rab interactor 1 controls neuronal plasticity by coordinating dendritic filopodial motility and AMPA receptor turnover
title_full_unstemmed Ras and Rab interactor 1 controls neuronal plasticity by coordinating dendritic filopodial motility and AMPA receptor turnover
title_short Ras and Rab interactor 1 controls neuronal plasticity by coordinating dendritic filopodial motility and AMPA receptor turnover
title_sort ras and rab interactor 1 controls neuronal plasticity by coordinating dendritic filopodial motility and ampa receptor turnover
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5231897/
https://www.ncbi.nlm.nih.gov/pubmed/27852895
http://dx.doi.org/10.1091/mbc.E16-07-0526
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