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Submitted on February 16, 2006
Accepted on April 4, 2006
Bruchpilot Promotes Active Zone Assembly, Ca2+-Channel Clustering, and Vesicle Release
Robert J. Kittel 1, Carolin Wichmann 2, Tobias M. Rasse 1, Wernher Fouquet 1, Manuela Schmidt 1, Andreas Schmid 1, Dhananjay A. Wagh 3, Christian Pawlu 4, Robert R. Kellner 5, Katrin I. Willig 5, Stefan W. Hell 5, Erich Buchner 3, Manfred Heckmann 4*, Stephan J. Sigrist 6*
1 European Neuroscience Institute Göttingen, Grisebachstr. 5, 37077 Göttingen, Germany. 2 European Neuroscience Institute Göttingen, Grisebachstr. 5, 37077 Göttingen, Germany; Institut für Klinische Neurobiologie, Josef-Schneider-Str. 11, 97080 Würzburg, Germany. 3 Lehrstuhl für Genetik und Neurobiologie, Am Hubland, 97074 Würzburg, Germany. 4 Institut für Klinische Neurobiologie, Josef-Schneider-Str. 11, 97080 Würzburg, Germany. 5 Max Planck Institute for Biophysical Chemistry, Department of NanoBiophotonics, Am Fassberg 11, 37077 Göttingen, Germany. 6 European Neuroscience Institute Göttingen, Grisebachstr. 5, 37077 Göttingen, Germany; Institut für Klinische Neurobiologie, Rudolf-Virchow-Zentrum, 97080 Würzburg, Germany.
* To whom correspondence should be addressed.
Manfred Heckmann , E-mail: Heckmann_M{at}klinik.uni-wuerzburg.de Stephan J. Sigrist , E-mail: ssigris{at}gwdg.de
The molecular organization of presynaptic active zones duringcalcium influx-triggered neurotransmitter release is the focusof intense investigation. The Drosophila coiled-coil domainprotein Bruchpilot (BRP) was observed in donut-shaped structurescentered at active zones of neuromuscular synapses using subdiffractionresolution STED (stimulated emission depletion) fluorescencemicroscopy. At brp mutant active zones, electron-dense projections(T-bars) were entirely lost, Ca2+-channels reduced in density,evoked vesicle release was depressed, and short-term plasticityaltered. BRP-like proteins seem to establish proximity betweenCa2+-channels and vesicles to allow efficient transmitter releaseand patterned synaptic plasticity.
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