The X-linked Mental Retardation Protein OPHN1 Interacts with Homer1b/c to Control Spine Endocytic Zone Positioning and Expression of Synaptic Potentiation

Nakano-Kobayashi, A., Tai, Y., Nadif Kasri, N., Van Aelst, L. (2014) The X-linked Mental Retardation Protein OPHN1 Interacts with Homer1b/c to Control Spine Endocytic Zone Positioning and Expression of Synaptic Potentiation. Journal of Neuroscience, 34 (26). pp. 8665-71. ISSN 0270-6474

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URL: http://www.ncbi.nlm.nih.gov/pubmed/24966368
DOI: 10.1523/jneurosci.0894-14.2014

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.

Item Type: Paper
Subjects: diseases & disorders > congenital hereditary genetic diseases > mental retardation
organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions > synapse
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > synaptic plasticity
CSHL Authors:
Communities: CSHL labs > Van Aelst lab
Depositing User: Matt Covey
Date Deposited: 11 Jul 2014 19:21
Last Modified: 09 Oct 2014 13:59
PMCID: PMC4069349
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30483

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