The release of neurotransmitter from active zones (AZs) of presynaptic terminals is one of the fundamental steps in chemical neurotransmission. Bruchpilot (BRP) is a key protein component of Drosophila AZs by promoting calcium channel clustering to ensure adequate transmitter release (Kittel et al., 2006). The hypomorphic brp^nude allele results in a truncated protein lacking the C-terminal 17 amino acids of BRP. Detailed analyses of brp^nude mutants reveal impaired vesicle tethering accompanied by short-term synaptic depression, altered sustained transmitter release, and a slowed recovery phase (Hallermann et al., 2010). As the molecular basis of these defects is unclear, we set out to test the hypothesis that neuronal expression of a peptide containing the BRP C-term (BRP^C17) would deliver a synaptic phenocopy of brp^nude by competitively binding the putative vesicular interaction partner of BRP. This hypothesis is strongly supported by our electrophysiological analysis of larval neuromuscular synapses. Inspired by this data we are currently studying consequences following tissue-specific expression of BRP^C17 peptide via several lines of investigation to substantiate our hypothesis.

Kittel RJ, Wichmann C, Rasse TM, Fouquet W, Schmidt M, Schmid A, Wagh DA, Pawlu C, Kellner RR, Willig KI, Hell SW, Buchner E, Heckmann M, Sigrist SJ (2006) Bruchpilot promotes active zone assembly, Ca²⁺ channel clustering, and vesicle release.Science312:1051–1054.

Hallermann S, Kittel RJ, Wichmann C, Weyhersmüller A, Fouquet W, Mertel S, Owald D, Eimer S, Depner H, Schwärzel M, Sigrist SJ, Heckmann M (2010c) Naked dense bodies provoke depression. J Neurosci 30:14340–14345.