Rabphilin potentiates soluble N-ethylmaleimide sensitive factor attachment protein receptor function independently of rab3.
Rabphilin, a putative rab effector, interacts specifically with the GTP-bound form of the synaptic vesicle-associated protein rab3a. In this study, we define in vivo functions for rabphilin through the characterization of mutants 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 mechanical stimulation. Furthermore, rabphilin mutations display strong synergistic interactions with hypomorphic lesions in the syntaxin, synaptosomal-associated protein of 25 kDa, and synaptobrevin soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) genes; double mutants were nonresponsive to mechanical stimulation. These synergistic interactions were independent of rab3 function and were not observed in rab3-SNARE double mutants. Our data reveal rab3-independent functions for rabphilin in the potentiation of SNARE function.
Staunton
J
J
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Ganetzky
B
B
Nonet
M L
ML
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D015415:Biomarkers; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D004594:Electrophysiology; D006160:Guanosine Triphosphate / Q000378:metabolism; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism; D008124:Locomotion / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D010812:Physical Stimulation; D017434:Protein Structure, Tertiary / Q000502:physiology; D050600:SNARE Proteins; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D012894:Sleep Stages / Q000235:genetics; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D013569:Synapses / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25; D033921:Vesicular Transport Proteins; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020692:rab3 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000097624:Rabphilin-3A
D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D006160:Guanosine Triphosphate; D015801:Helminth Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050600:SNARE Proteins; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D050825:Synaptosomal-Associated Protein 25; D033921:Vesicular Transport Proteins; D020691:rab GTP-Binding Proteins; D020692:rab3 GTP-Binding Proteins; D000097624:Rabphilin-3A; C443319:rbf-1 protein, C elegans