ARHGAP12 functions as a developmental brake on excitatory synapse function

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

    Research output: Contribution to journalArticleAcademicpeer-review

    9 Citations (Scopus)
    45 Downloads (Pure)

    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.
    Original languageEnglish
    Pages (from-to)1355-1368
    Number of pages14
    JournalCell reports
    Volume14
    Issue number6
    DOIs
    Publication statusPublished - 16 Feb 2016

      Fingerprint

    Cite this

    Ba, W., Selten, M. M., van der Raadt, J., van Veen, H., Li, L-L., Benevento, M., ... Nadif Kasri, N. (2016). ARHGAP12 functions as a developmental brake on excitatory synapse function. Cell reports, 14(6), 1355-1368. https://doi.org/10.1016/j.celrep.2016.01.037