title: ARHGAP12 Functions as a Developmental Brake on Excitatory Synapse Function.
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.
authors: 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.
authors: W
authors: W
authors: Ba
authors: 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.
authors: M M
authors: MM
authors: Selten
authors: Department of Human Genetics, Radboudumc, 6500 HB Nijmegen, the Netherlands; Radboud Institute for Molecular Life Sciences, Radboudumc, 6525 GA Nijmegen, the Netherlands.
authors: J
authors: J
authors: van der Raadt
authors: 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.
authors: H
authors: H
authors: van Veen
authors: Molecular Signalling Laboratory, Department of Neurobiology, A.I. Virtanen Institute, University of Eastern Finland, Kuopio 70210, Finland.
authors: L-L
authors: LL
authors: Li
authors: 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.
authors: M
authors: M
authors: Benevento
authors: 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.
authors: A R
authors: AR
authors: Oudakker
authors: Department of Human Genetics, Radboudumc, 6500 HB Nijmegen, the Netherlands.
authors: R S E
authors: RSE
authors: Lasabuda
authors: Department of Human Genetics, Radboudumc, 6500 HB Nijmegen, the Netherlands; Radboud Institute for Molecular Life Sciences, Radboudumc, 6525 GA Nijmegen, the Netherlands.
authors: S J
authors: SJ
authors: Letteboer
authors: Department of Human Genetics, Radboudumc, 6500 HB Nijmegen, the Netherlands; Radboud Institute for Molecular Life Sciences, Radboudumc, 6525 GA Nijmegen, the Netherlands.
authors: R
authors: R
authors: Roepman
authors: 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.
authors: R J A
authors: RJA
authors: van Wezel
authors: 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.
authors: M J
authors: MJ
authors: Courtney
authors: 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.
authors: H
authors: H
authors: van Bokhoven
authors: 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.
authors: N
authors: N
authors: Nadif Kasri
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000378:metabolism; D049229:Dendritic Spines / Q000502:physiology / Q000648:ultrastructure; D004622:Embryo, Mammalian; D004705:Endocytosis; D020690:GTPase-Activating Proteins / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D015778:Minor Histocompatibility Antigens / Q000235:genetics* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D061251:Primary Cell Culture; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000235:genetics* / Q000378:metabolism; D059010:Single-Cell Analysis; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D009435:Synaptic Transmission; D046509:Tissue Culture Techniques
chemical_list: D020690:GTPase-Activating Proteins; D008869:Microtubule-Associated Proteins; D015778:Minor Histocompatibility Antigens; D018091:Receptors, AMPA; C498640:Trip10 protein, rat