title: Ras and Rab interactor 1 controls neuronal plasticity by coordinating dendritic filopodial motility and AMPA receptor turnover.
abstract: 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.
authors.affiliation: Department of Physiology and Neurobiology, Eötvös Loránd University, H-1117 Budapest, Hungary.
authors.forename: Zsófia
authors.initials: Z
authors.lastname: Szíber
authors.affiliation: Department of Physiology and Neurobiology, Eötvös Loránd University, H-1117 Budapest, Hungary.
authors.forename: Hanna
authors.initials: H
authors.lastname: Liliom
authors.affiliation: Institute of Cell Biology and Immunology, University of Stuttgart, D-70569 Stuttgart, Germany.
authors.forename: Carlos O Oueslati
authors.initials: CO
authors.lastname: Morales
authors.affiliation: Department of Physiology and Neurobiology, Eötvös Loránd University, H-1117 Budapest, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Ignácz
authors.affiliation: Department of Physiology and Neurobiology, Eötvös Loránd University, H-1117 Budapest, Hungary.
authors.forename: Anikó Erika
authors.initials: AE
authors.lastname: Rátkai
authors.affiliation: Institute of Cell Biology and Immunology, University of Stuttgart, D-70569 Stuttgart, Germany.
authors.forename: Kornelia
authors.initials: K
authors.lastname: Ellwanger
authors.affiliation: Institute of Cell Biology and Immunology, University of Stuttgart, D-70569 Stuttgart, Germany.
authors.forename: Gisela
authors.initials: G
authors.lastname: Link
authors.affiliation: MTA-ELTE-NAP B Neuronal Cell Biology Research Group, H-1117 Budapest, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Szűcs
authors.affiliation: Institute of Cell Biology and Immunology, University of Stuttgart, D-70569 Stuttgart, Germany.|Stuttgart Research Center Systems Biology, University of Stuttgart, D-70569 Stuttgart, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Hausser
authors.affiliation: Department of Physiology and Neurobiology, Eötvös Loránd University, H-1117 Budapest, Hungary schlett.katalin@ttk.elte.hu.|MTA-ELTE-NAP B Neuronal Cell Biology Research Group, H-1117 Budapest, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Schlett
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology; D003712:Dendrites / Q000378:metabolism / Q000502:physiology; D004705:Endocytosis / Q000502:physiology; D006624:Hippocampus / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism / Q000502:physiology; D018091:Receptors, AMPA / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013570:Synaptic Membranes / Q000502:physiology; D020691:rab GTP-Binding Proteins / Q000378:metabolism* / Q000502:physiology*; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D018091:Receptors, AMPA; C490451:Rin1 protein, mouse; D016315:Proto-Oncogene Proteins c-abl; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins