title: The X-linked mental retardation protein OPHN1 interacts with Homer1b/c to control spine endocytic zone positioning and expression of synaptic potentiation.
abstract: At glutamatergic synapses, local endocytic recycling of AMPA receptors (AMPARs) is important for the supply of a mobile pool of AMPARs required for synaptic potentiation. This local recycling of AMPARs critically relies on the presence of an endocytic zone (EZ) near the postsynaptic density (PSD). The precise mechanisms that couple the EZ to the PSD still remain largely elusive, with the large GTPase Dynamin-3 and the multimeric PSD adaptor protein Homer1 as the two main players identified. Here, we demonstrate that a physical interaction between the X-linked mental retardation protein oligophrenin-1 (OPHN1) and Homer1b/c is crucial for the positioning of the EZ adjacent to the PSD, and present evidence that this interaction is important for OPHN1's role in controlling activity-dependent strengthening of excitatory synapses in the rat hippocampus. Disruption of the OPHN1-Homer1b/c interaction causes a displacement of EZs from the PSD, along with impaired AMPAR recycling and reduced AMPAR accumulation at synapses, in both basal conditions and conditions that can induce synaptic potentiation. Together, our findings unveil a novel role for OPHN1 as an interaction partner of Homer1b/c in spine EZ positioning, and provide new mechanistic insight into how genetic deficits in OPHN1 can lead to impaired synapse maturation and plasticity.
authors: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724.
authors: Akiko
authors: A
authors: Nakano-Kobayashi
authors: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724.
authors: Yilin
authors: http://orcid.org/0000-0001-7210-240X
authors: Y
authors: Tai
authors: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724 vanaelst@cshl.edu n.nadif@donders.ru.nl.
authors: Nael
authors: N
authors: Nadif Kasri
authors: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724 vanaelst@cshl.edu n.nadif@donders.ru.nl.
authors: Linda
authors: http://orcid.org/0000-0002-0870-012X
authors: L
authors: Van Aelst
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D049229:Dendritic Spines / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D000072233:Homer Scaffolding Proteins; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D020690:GTPase-Activating Proteins; D000072233:Homer Scaffolding Proteins; C000606624:Homer1 protein, rat; D009687:Nuclear Proteins; C529605:OPHN1 protein, rat; D018091:Receptors, AMPA
keywords: Rho-GAP; endocytic zone; mental retardation; synaptic potentiation