RT Journal Article
SR Electronic
T1 The X-linked Mental Retardation Protein OPHN1 Interacts with Homer1b/c to Control Spine Endocytic Zone Positioning and Expression of Synaptic Potentiation
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8665
OP 8671
DO 10.1523/JNEUROSCI.0894-14.2014
VO 34
IS 26
A1 Akiko Nakano-Kobayashi
A1 Yilin Tai
A1 Nael Nadif Kasri
A1 Linda Van Aelst
YR 2014
UL http://www.jneurosci.org/content/34/26/8665.abstract
AB 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.