Rab proteins are Ras-like small GTPases that play a critical role in the regulation of the intracellular vesicle trafficking in the exocytosis and endocytosis pathways. Over 60 Rab proteins have been identified in mammalian cells, and they display a characteristic pattern of subcellular localization. Rab proteins are posttranslationally modified by lipid at their C-terminus, and this modification is essential for their membrane association and function. The Rab escort protein (REP) and the Rab geranygeranyltransferase (RabGGT) cooperatively function for this protein modification by directly interacting with each Rab proteins. Mutations in human Rep1 gene are known to specifically cause an X-linked retinal degeneration called choroideremia. However, no mutation has been found in the GGT gene, it is not clear how these two molecules contribute to Rab protein modification, what kind of genetic hierarchy regulates each protein functions. In this study, we show the evidences that C. elegans REP-1 may functions in the specific Rab pathways and in the specific tissues. We have isolated a missense mutant (
ta208) of the C. elegans
rep-1 gene from the screening toward a reduced response to melatonin, which decreases neuronal activity in C. elegans. The
rep-1(
ta208) mutant animals do not show gross morphological abnormalities, except for a small number of progeny. To know the neuronal roles of REP-1 and the relationship with each Rab protein, we first examined drug sensitivities in the
rep-1(
ta208) mutants because both
rab-3 and
rab-27 mutants show resistance to aldicarb, an inhibitor of acetylcholinesterase.
rep-1 mutants were mildly resistant to aldicarb, but not to levamisole, an agonist for Acetylcholine receptors, suggesting reduced transmitter release from presynaptic terminals. Double mutant analyses with
rab-3 or
rab-27 suggest that
rep-1 and
rab-27 may function in the same pathway, and that this REP-1/RAB-27 pathway is parallel with the RAB-3 pathway for synaptic transmission at NMJ. However, both
rep-1(
ta208) mutants and
rep-1(RNAi) worms did not show severe defects in the defecation behaviors, compared to severe defects in
rab-27 mutants and RabGGT RNAi worms. Thus, our results suggest that REP-1 seems to function in the specific Rab pathways in the specific tissues, or that the requirement of REP-1 may not the same for each Rab proteins.
rep-1 gene was expressed in several tissues including many neurons and the intestine. We are now investigating whether subcellular localizations of Rab proteins including endocytic Rabs are affected in
rep-1 mutants or
rep-1(RNAi) worms.