Rabphilin potentiates soluble N-ethylmaleimide sensitive factor attachmentprotein receptor function independently of rab3

Rabphilin, a putative rab effector, interacts specifically with the GTP-bou nd form of the synaptic vesicle-associated protein rab3a. In this study, we define in vivo functions for rabphilin through the characterization of mut ants that disrupt the Caenorhabditis elegans rabphilin homolog. The mutants do not display the general synaptic defects associated with rab3 lesions, as assayed at the pharmacological, physiological, and ultrastructural level . However, rabphilin mutants exhibit severe lethargy in the absence of mech anical stimulation. Furthermore, rabphilin mutations display strong synergi stic interactions with hypomorphic lesions in the syntaxin, synaptosomal-as sociated protein of 25 kDa, and synaptobrevin soluble N-ethylmaleimide sens itive factor attachment protein receptor (SNARE) genes; double mutants were nonresponsive to mechanical stimulation. These synergistic interactions we re independent of rab3 function and were not observed in rab3-SNARE double mutants. Our data reveal rab3-independent functions for rabphilin in the po tentiation of SNARE function.