Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

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}charite.de (D.S.); stephan.sigrist{at}fu-berlin.de (S.J.S.)


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Synaptic vesicle recycling: steps and principles.
S. O. Rizzoli (2014)
EMBO J. 33, 788-822
   Abstract »    Full Text »    PDF »
Developmental refinement of hair cell synapses tightens the coupling of Ca2+ influx to exocytosis.
A. B. Wong, M. A. Rutherford, M. Gabrielaitis, T. Pangrsic, F. Gottfert, T. Frank, S. Michanski, S. Hell, F. Wolf, C. Wichmann, et al. (2014)
EMBO J. 33, 247-264
   Abstract »    Full Text »    PDF »
Defects in Synapse Structure and Function Precede Motor Neuron Degeneration in Drosophila Models of FUS-Related ALS.
M. Shahidullah, S. J. Le Marchand, H. Fei, J. Zhang, U. B. Pandey, M. B. Dalva, P. Pasinelli, and I. B. Levitan (2013)
J. Neurosci. 33, 19590-19598
   Abstract »    Full Text »    PDF »
New Approaches for Studying Synaptic Development, Function, and Plasticity Using Drosophila as a Model System.
C. A. Frank, X. Wang, C. A. Collins, A. A. Rodal, Q. Yuan, P. Verstreken, and D. K. Dickman (2013)
J. Neurosci. 33, 17560-17568
   Abstract »    Full Text »    PDF »
Cell biology in neuroscience: Cellular and molecular mechanisms underlying presynapse formation.
P. H. Chia, P. Li, and K. Shen (2013)
J. Cell Biol. 203, 11-22
   Abstract »    Full Text »    PDF »
The Bruchpilot cytomatrix determines the size of the readily releasable pool of synaptic vesicles.
T. Matkovic, M. Siebert, E. Knoche, H. Depner, S. Mertel, D. Owald, M. Schmidt, U. Thomas, A. Sickmann, D. Kamin, et al. (2013)
J. Cell Biol. 202, 667-683
   Abstract »    Full Text »    PDF »
Inter-channel scaffolding of presynaptic CaV2.2 via the C terminal PDZ ligand domain.
S. R. Gardezi, Q. Li, and E. F. Stanley (2013)
Biology Open 2, 492-498
   Abstract »    Full Text »    PDF »
Fife, a Drosophila Piccolo-RIM Homolog, Promotes Active Zone Organization and Neurotransmitter Release.
J. J. Bruckner, S. J. Gratz, J. K. Slind, R. R. Geske, A. M. Cummings, S. E. Galindo, L. K. Donohue, and K. M. O'Connor-Giles (2012)
J. Neurosci. 32, 17048-17058
   Abstract »    Full Text »    PDF »
RIM Controls Homeostatic Plasticity through Modulation of the Readily-Releasable Vesicle Pool.
M. Muller, K. S. Y. Liu, S. J. Sigrist, and G. W. Davis (2012)
J. Neurosci. 32, 16574-16585
   Abstract »    Full Text »    PDF »
RIM Promotes Calcium Channel Accumulation at Active Zones of the Drosophila Neuromuscular Junction.
E. R. Graf, V. Valakh, C. M. Wright, C. Wu, Z. Liu, Y. Q. Zhang, and A. DiAntonio (2012)
J. Neurosci. 32, 16586-16596
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882