A1 Refereed original research article in a scientific journal

ARHGAP12 Functions as a Developmental Brake on Excitatory Synapse Function




AuthorsBa W, Selten MM, van der Raadt J, van Veen H, Li LL, Benevento M, Oudakker AR, Lasabuda RSE, Letteboer SJ, Roepman R, van Wezel RJA, Courtney MJ, van Bokhoven H, Kasri NN

PublisherCELL PRESS

Publication year2016

JournalCell Reports

Journal name in sourceCELL REPORTS

Journal acronymCELL REP

Volume14

Issue6

First page 1355

Last page1368

Number of pages14

ISSN2211-1247

DOIhttps://doi.org/10.1016/j.celrep.2016.01.037(external)

Web address http://www.cell.com/cell-reports/fulltext/S2211-1247%2816%2900058-9(external)


Abstract

The molecular mechanisms that promote excitatory synapse development have been extensively studied. However, the molecular events preventing precocious excitatory synapse development so that synapses form at the correct time and place are less well understood. Here, we report the functional characterization of ARHGAP12, a previously uncharacterized Rho GTPase-activating protein (RhoGAP) in the brain. ARHGAP12 is specifically expressed in the CA1 region of the hippocampus, where it localizes to the postsynaptic compartment of excitatory synapses. ARHGAP12 negatively controls spine size via its RhoGAP activity and promotes, by interacting with CIP4, postsynaptic AMPA receptor endocytosis. Arhgap12 knockdown results in precocious maturation of excitatory synapses, as indicated by a reduction in the proportion of silent synapses. Collectively, our data show that ARHGAP12 is a synaptic RhoGAP that regulates excitatory synaptic structure and function during development.




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