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

• Published in: Science (American Association for the Advancement of Science) 2006-05, Vol.312 (5776), p.1051-1054
• Main Authors: Kittel, Robert J, Wichmann, Carolin, Rasse, Tobias M, Fouquet, Wernher, Schmidt, Manuela, Schmid, Andreas, Wagh, Dhananjay A, Pawlu, Christian, Kellner, Robert R, Willig, Katrin I, Hell, Stefan W, Buchner, Erich, Heckmann, Manfred, Sigrist, Stephan J
• Format: Article
• Language: English
• Subjects: Action Potentials; Animals; Biological and medical sciences; Brunchpilot protein; Calcium; calcium channels; Calcium Channels - metabolism; Cell membranes. Ionic channels. Membrane pores; Cell structures and functions; cytochemistry; Drosophila; Drosophila melanogaster; Drosophila Proteins - genetics; Drosophila Proteins - physiology; Electric current; Female; Fundamental and applied biological sciences. Psychology; Glutamate receptors; insect proteins; Insects; Larva; Male; Microscopy; Models, Neurological; Molecular and cellular biology; Mutation; Nerve Tissue Proteins - metabolism; Nerve Tissue Proteins - physiology; Neurons; neurophysiology; Neuroscience; Neurosciences; neurotransmitter release; Neurotransmitters; Presynaptic Terminals - metabolism; Proteins; Receptors; synapse; Synapses; Synapses - metabolism; Synapses - physiology; Synapses - ultrastructure; synaptic transmission; Synaptic Vesicles - metabolism
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1126308

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.