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Science 334 (6062): 1565-1569

Copyright © 2011 by the American Association for the Advancement of Science

RIM-Binding Protein, a Central Part of the Active Zone, Is Essential for Neurotransmitter Release

Karen S. Y. Liu,1,* Matthias Siebert,2,* Sara Mertel,1,* Elena Knoche,2,* Stephanie Wegener,2,* Carolin Wichmann,2 Tanja Matkovic,1 Karzan Muhammad,1 Harald Depner,1 Christoph Mettke,1 Johanna Bückers,3 Stefan W. Hell,3 Martin Müller,4 Graeme W. Davis,4 Dietmar Schmitz,2,5,{dagger} Stephan J. Sigrist1,2,{dagger}

Abstract: The molecular machinery mediating the fusion of synaptic vesicles (SVs) at presynaptic active zone (AZ) membranes has been studied in detail, and several essential components have been identified. AZ-associated protein scaffolds are viewed as only modulatory for transmission. We discovered that Drosophila Rab3-interacting molecule (RIM)–binding protein (DRBP) is essential not only for the integrity of the AZ scaffold but also for exocytotic neurotransmitter release. Two-color stimulated emission depletion microscopy showed that DRBP surrounds the central Ca2+ channel field. In drbp mutants, Ca2+ channel clustering and Ca2+ influx were impaired, and synaptic release probability was drastically reduced. Our data identify RBP family proteins as prime effectors of the AZ scaffold that are essential for the coupling of SVs, Ca2+ channels, and the SV fusion machinery.

1 Department of Genetics, Institute for Biology, Free University Berlin, 14195 Berlin, Germany.
2 NeuroCure Cluster of Excellence, Charité Berlin, Charitéplatz 1, 10117 Berlin, Germany.
3 Department of Nanobiophotonics, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
4 Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94158, USA.
5 DZNE—German Center for Neurodegenerative Diseases, 10117 Berlin, Germany.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: dietmar.schmitz{at} (D.S.); stephan.sigrist{at} (S.J.S.)

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