Cysteine string proteins and presynaptic function.

A brief review is presented of investigations of a novel family of synaptic vesicle proteins, the cysteine string proteins (csps). Studies of csp mutants in Drosophila reveal that csps are crucial components of the excitation-secretion machinery at nerve terminals. Current data cannot distinguish between a primary role of csps in modulating calcium ion influx at the nerve terminal versus a more-direct role in the exocytotic cascade. In this context, the remarkable post-translational modification of csps, namely the fatty acylation of as many as 12 of the 13 cysteine residues of the Torpedo protein, suggests that csps may participate more directly in the process of membrane fusion that underlies exocytosis. This would be achieved by using the fatty acyl chains of the csps as templates for 'lipid flow' that would allow the fusion of vesicular and plasma membranes. These hypotheses provide a useful framework for empirical tests of the role of csps in nerve terminal function.