ARHGAP12 Functions as a Developmental Brake on Excitatory Synapse Function.

Autor:	Ba W; Department of Cognitive Neuroscience, Radboudumc, 6500 HB Nijmegen, the Netherlands; Department of Human Genetics, Radboudumc, 6500 HB Nijmegen, the Netherlands; Donders Institute for Brain, Cognition, and Behaviour, 6525 AJ Nijmegen, the Netherlands., Selten MM; Department of Cognitive Neuroscience, Radboudumc, 6500 HB Nijmegen, the Netherlands; Department of Human Genetics, Radboudumc, 6500 HB Nijmegen, the Netherlands; Donders Institute for Brain, Cognition, and Behaviour, 6525 AJ Nijmegen, the Netherlands., van der Raadt J; Department of Human Genetics, Radboudumc, 6500 HB Nijmegen, the Netherlands; Radboud Institute for Molecular Life Sciences, Radboudumc, 6525 GA Nijmegen, the Netherlands., van Veen H; Donders Institute for Brain, Cognition, and Behaviour, 6525 AJ Nijmegen, the Netherlands; Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, P.O. Box 80082, 30508 TB Utrecht, the Netherlands., Li LL; Molecular Signalling Laboratory, Department of Neurobiology, A.I. Virtanen Institute, University of Eastern Finland, Kuopio 70210, Finland., Benevento M; Department of Cognitive Neuroscience, Radboudumc, 6500 HB Nijmegen, the Netherlands; Department of Human Genetics, Radboudumc, 6500 HB Nijmegen, the Netherlands; Donders Institute for Brain, Cognition, and Behaviour, 6525 AJ Nijmegen, the Netherlands., Oudakker AR; Department of Cognitive Neuroscience, Radboudumc, 6500 HB Nijmegen, the Netherlands; Department of Human Genetics, Radboudumc, 6500 HB Nijmegen, the Netherlands; Donders Institute for Brain, Cognition, and Behaviour, 6525 AJ Nijmegen, the Netherlands., Lasabuda RSE; Department of Human Genetics, Radboudumc, 6500 HB Nijmegen, the Netherlands., Letteboer SJ; Department of Human Genetics, Radboudumc, 6500 HB Nijmegen, the Netherlands; Radboud Institute for Molecular Life Sciences, Radboudumc, 6525 GA Nijmegen, the Netherlands., Roepman R; Department of Human Genetics, Radboudumc, 6500 HB Nijmegen, the Netherlands; Radboud Institute for Molecular Life Sciences, Radboudumc, 6525 GA Nijmegen, the Netherlands., van Wezel RJA; Donders Institute for Brain, Cognition, and Behaviour, 6525 AJ Nijmegen, the Netherlands; Biomedical Signal and Systems, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, 7500 AE Enschede, the Netherlands., Courtney MJ; Molecular Signalling Laboratory, Department of Neurobiology, A.I. Virtanen Institute, University of Eastern Finland, Kuopio 70210, Finland; Turku Centre for Biotechnology, Abo Akademi University and University of Turku, Turku 20521, Finland., van Bokhoven H; Department of Cognitive Neuroscience, Radboudumc, 6500 HB Nijmegen, the Netherlands; Department of Human Genetics, Radboudumc, 6500 HB Nijmegen, the Netherlands; Donders Institute for Brain, Cognition, and Behaviour, 6525 AJ Nijmegen, the Netherlands; Radboud Institute for Molecular Life Sciences, Radboudumc, 6525 GA Nijmegen, the Netherlands., Nadif Kasri N; Department of Cognitive Neuroscience, Radboudumc, 6500 HB Nijmegen, the Netherlands; Department of Human Genetics, Radboudumc, 6500 HB Nijmegen, the Netherlands; Donders Institute for Brain, Cognition, and Behaviour, 6525 AJ Nijmegen, the Netherlands. Electronic address: n.nadif@donders.ru.nl.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2016 Feb 16; Vol. 14 (6), pp. 1355-1368. Date of Electronic Publication: 2016 Feb 04.
DOI:	10.1016/j.celrep.2016.01.037
Abstrakt:	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. (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu