The Rho-Linked Mental Retardation Protein OPHN1 Controls Synaptic Vesicle Endocytosis via Endophilin A1

Nakano-Kobayashi, A., Nadif Kasri, N., Newey, S. E., Van Aelst, L. (July 2009) The Rho-Linked Mental Retardation Protein OPHN1 Controls Synaptic Vesicle Endocytosis via Endophilin A1. Curr Biol, 19 (13). 1133-1139 .

URL: http://www.ncbi.nlm.nih.gov/pubmed/19481455
DOI: 10.1016/j.cub.2009.05.022

Abstract

Summary Neurons transmit information at chemical synapses by releasing neurotransmitters that are stored in synaptic vesicles (SVs) at the presynaptic site. After release, these vesicles need to be efficiently retrieved in order to maintain synaptic transmission [1], [2] and [3]. In concurrence, malfunctions in SV recycling have been associated with cognitive disorders [4] and [5]. Oligophrenin-1 (OPHN1) encodes a Rho-GTPase-activating protein (Rho-GAP) whose loss of function causes X-linked mental retardation [6] and [7]. OPHN1 is highly expressed in the brain and present both pre- and postsynaptically in neurons [8]. Previous studies report that postsynaptic OPHN1 is important for dendritic spine morphogenesis [8] and [9], but its function at the presynaptic site remains largely unexplored. Here, we present evidence that reduced or defective OPHN1 signaling impairs SV cycling at hippocampal synapses. In particular, we show that OPHN1 knockdown affects the kinetic efficiency of endocytosis. We further demonstrate that OPHN1 forms a complex with endophilin A1, a protein implicated in membrane curvature generation during SV endocytosis [10], [11], [12], [13], [14], [15] and [16] and, importantly, that OPHN1's interaction with endophilin A1 and its Rho-GAP activity are important for its function in SV endocytosis. Our findings suggest that defects in efficient SV retrieval may contribute to the pathogenesis of OPHN1-linked cognitive impairment.

Item Type: Paper
Uncontrolled Keywords: CELLBIO MOLNEURO HUMDISEASE
Subjects: diseases & disorders > congenital hereditary genetic diseases > mental retardation
organs, tissues, organelles, cell types and functions
organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions
organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions > synapse
CSHL Authors:
Communities: CSHL labs > Van Aelst lab
CSHL Cancer Center Shared Resources > Animal Services
CSHL Cancer Center Shared Resources > DNA Sequencing Service
CSHL Cancer Center Shared Resources > Instrumentation Service
CSHL Cancer Center Shared Resources > Microscopy Service
Depositing User: Matt Covey
Date: 14 July 2009
Date Deposited: 20 Feb 2013 14:28
Last Modified: 30 Dec 2014 16:28
PMCID: PMC2711225
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27445

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