ARHGAP12 Functions as a Developmental Brake on Excitatory Synapse Function

Publication date: Available online 4 February 2016
Source:Cell Reports
Author(s): W. Ba, M.M. Selten, J. van der Raadt, H. van Veen, L.-L. Li, M. Benevento, A.R. Oudakker, R.S.E. Lasabuda, S.J. Letteboer, R. Roepman, R.J.A. van Wezel, M.J. Courtney, H. van Bokhoven, N. Nadif Kasri
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.

Graphical abstract

Teaser

Ba et al. find that the Rac1 GAP, ARHGAP12, coordinates dendritic spine morphology and synaptic strength via its GAP activity and interaction with CIP4, respectively. ARHGAP12 limits synapse maturation by restricting silent synapses converting to functional synapses in the developing hippocampus.


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