PRESYNAPTIC DYSFUNCTION IN DROSOPHILA CSP MUTANTS

Cysteine string proteins are synapse-specific proteins. In Drosophila, csp deletion mutants exhibit temperature-sensitive paralysis and earl y death. Here, we report that neuromuscular transmission is impaired p resynaptically in these csp mutant larvae. At 22 degrees C, evoked tra nsmitter release is depressed relative to wild type and rescued contro ls, and high frequency stimulation of the nerve leads to sporadic fail ures. At 30 degrees C, stimulus-evoked responses decline gradually bef ore failing completely. When the temperature is returned to 22 degrees C, evoked responses recover. Spontaneous release events persist at bo th 22 degrees C and 30 degrees C. Since nerve conduction and postsynap tic sensitivity are unaffected, these data indicate that csp mutations disrupt depolarization-secretion coupling. This disruption explains t he cellular basis of the temperature-sensitive paralysis of these orga nisms.