Function of STIM1 in C. elegans Ca 2+ signaling pathways

Plasma membrane store‐operated Ca 2+ channels (SOCs) are activated by depletion of intracellular Ca 2+ stores. While SOCs are thought to function in store refilling, their precise roles in Ca 2+ signaling in most cell types remains unclear. Recently, STIM1 was identified as a key regulatory component of SOC activity in mammals and Drosophila and is thought to function as an ER Ca 2+ sensor. The C. elegans genome encodes a single STIM1 homolog. We have undertaken a detailed characterization of C. elegans STIM1 to define the physiological functions of SOCs and the components of STIM1/SOC regulatory pathways. RNAi knockdown of STIM1 activity inhibits SOC activation in cultured intestinal epithelial cells. However, systemic knockdown of STIM1 by RNAi feeding has no effect on the worm defecation cycle, a process that is controlled by IP 3 –dependent Ca 2+ oscillations in the intestinal epithelium. In contrast, STIM1 RNAi induced complete sterility that was partially suppressed by a loss‐of‐function mutation in rrf‐1 indicating that the protein functions in somatic rather than germ cells. Video microscopy analysis of worms demonstrated that STIM1 knockdown disrupts ovulatory contractions of gonad sheath cells and dilation of the spermatheca‐gonad valve. Sheath cell and spermatheca contractile activity are required for ovulation and are controlled by IP 3 –dependent Ca 2+ signaling mechanisms. Our results demonstrate that STIM1 regulates C. elegans SOC activity and that SOC channels are required for some but not all Ca 2+ ‐dependent physiological processes in the worm. Ongoing reverse and forward genetic analyses are focused on defining STIM1 signaling mechanisms.