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Science 312 (5776): 1051-1054

Copyright © 2006 by the American Association for the Advancement of Science

Bruchpilot Promotes Active Zone Assembly, Ca2+ Channel Clustering, and Vesicle Release

Robert J. Kittel,1* Carolin Wichmann,1,2* Tobias M. Rasse,1* Wernher Fouquet,1 Manuela Schmidt,1 Andreas Schmid,1 Dhananjay A. Wagh,3 Christian Pawlu,2 Robert R. Kellner,4 Katrin I. Willig,4 Stefan W. Hell,4 Erich Buchner,3 Manfred Heckmann,2{dagger} Stephan J. Sigrist1,5{dagger}

Abstract: The molecular organization of presynaptic active zones during calcium influx–triggered neurotransmitter release is the focus of intense investigation. The Drosophila coiled-coil domain protein Bruchpilot (BRP) was observed in donut-shaped structures centered at active zones of neuromuscular synapses by using subdiffraction resolution STED (stimulated emission depletion) fluorescence microscopy. At brp mutant active zones, electron-dense projections (T-bars) were entirely lost, Ca2+ channels were reduced in density, evoked vesicle release was depressed, and short-term plasticity was altered. BRP-like proteins seem to establish proximity between Ca2+ channels and vesicles to allow efficient transmitter release and patterned synaptic plasticity.

1 European Neuroscience Institute Göttingen, Grisebachstrasse 5, 37077 Göttingen, Germany.
2 Institut für Klinische Neurobiologie, Josef Schneider Strasse 11, 97080 Würzburg, Germany.
3 Lehrstuhl für Genetik und Neurobiologie, Am Hubland, 97074 Würzburg, Germany.
4 Department of Nano-Biophotonics, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
5 Institut für Klinische Neurobiologie, Rudolf Virchow Zentrum, 97080 Würzburg, Germany.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: Heckmann_M{at}klinik.uni-wuerzburg.de (M.H.); ssigris{at}gwdg.de (S.J.S.)

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