Making Babies with PAM and RAB: Investigating New Paradigms in Vesicular-Mediated Signaling Pathways

The nematode Caenorhabditis elegans is an excellent model organism for the study of signaling pathways in eukaryotes. These organisms, while comparatively simple, accurately exhibit many similar modes of cellular communication that our own cells utilize. We are investigating the role of PAM-1, an aminopeptidase, in a signaling pathway that governs gametogenesis. Adult worms homozygous for pam-1 mutations only produce a small number of progeny the majority of which are inviable. Expression of a transgenic PAM-1:GFP fusion protein reveals that PAM-1 functions in the somatic sheath cells of the gonad and stimulates maturation of oocytes in the germ line. Electron micrograph analysis of the sheath cells reveals a tissue enriched with large numbers of vesicles. This suggests that the signaling pathway through which PAM-1 affects the maturation of the oocytes within the gonad may be facilitated through vesicular transport of signal molecules from the sheath cells to the germline. The RAB family of small GTPases are integral to vesicular functioning in all eukaryotes; the C. elegans genome harbors 22 rab genes. We hypothesize that by shutting down specific rab genes by RNA interference (RNAi) in the compromised pam-1 background we will observe a synergistic effect on fecundity, establishing a novel relationship between PAM-1, RAB proteins, and a vesicular-mediated signaling pathway