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Kittel, R.J. et al. Bruchpilot promotes active zone assembly, Ca2+ channel clustering, and vesicle release. Science 312, 1051-1054

European Neuroscience Institute Göttingen, Grisebachstrasse 5, 37077 Göttingen, Germany.
Science (Impact Factor: 31.48). 06/2006; 312(5776):1051-4. DOI: 10.1126/science.1126308
Source: PubMed

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.

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    • "(M,M′) High-magnification imaging of Brp short ::GFP in the midline region of the main commissure. Both discrete small puncta in the size range of single active zones of NMJs (Kittel et al., 2006 "
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    • "DEVELOPMENT AZs in dysc and slo mutants facilitate enhanced spontaneous vesicle fusion. The BRP ring-like complex within the AZ surrounds a central core of VGCCs (Kittel et al., 2006). "
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    • "The AZ membrane is associated with an electron-dense protein matrix, termed the cytomatrix of the active zone (CAZ), that is partially resistant to detergent extraction (Phillips et al., 2001). CAZ components (Gundelfinger and Fejtova, 2012) include giant multidomain proteins such as piccolo, bassoon, ELKS (also termed CAST), relatives of Drosophila bruchpilot (BRP) (Kittel et al., 2006) and Fife (Bruckner et al., 2012), Rab3 interacting molecules (RIMs) (Kaeser et al., 2011), RIM binding proteins (RBPs) (Liu et al., 2011), Munc13, liprins, and G protein coupled receptor kinase 2 interacting protein (GIT) (Kim et al., 2003). Endocytic retrieval of exocytosed SV proteins involves adaptor proteins (Dittman and Ryan, 2009) such as AP-2, stonins (Fergestad and Broadie, 2001; Mullen et al., 2012), and AP180 (Koo et al., 2011). "
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