title: Physiological roles of STIM1 and Orai1 homologs and CRAC channels in the genetic model organism Caenorhabditis elegans.
abstract: The nematode Caenorhabditis elegans provides numerous experimental advantages for developing an integrative molecular understanding of physiological processes and has proven to be a valuable model for characterizing Ca(2+) signaling mechanisms. This review will focus on the role of Ca(2+) release activated Ca(2+) (CRAC) channel activity in function of the worm gonad and intestine. Inositol 1,4,5-trisphosphate (IP(3))-dependent oscillatory Ca(2+) signaling regulates contractile activity of the gonad and rhythmic posterior body wall muscle contraction (pBoc) required for ovulation and defecation, respectively. The C. elegans genome contains a single homolog of both STIM1 and Orai1, proteins required for CRAC channel function in mammalian and Drosophila cells. C. elegans STIM-1 and ORAI-1 are coexpressed in the worm gonad and intestine and give rise to robust CRAC channel activity when coexpressed in HEK293 cells. STIM-1 or ORAI-1 knockdown causes complete sterility demonstrating that the genes are essential components of gonad Ca(2+) signaling. Knockdown of either protein dramatically inhibits intestinal cell CRAC channel activity, but surprisingly has no effect on pBoc, intestinal Ca(2+) oscillations or intestinal ER Ca(2+) store homeostasis. CRAC channels thus do not play obligate roles in all IP(3)-dependent signaling processes in C. elegans. Instead, we suggest that CRAC channels carry out highly specialized and cell specific signaling roles and that they may function as a failsafe mechanism to prevent Ca(2+) store depletion under pathophysiological and stress conditions.
authors: Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232-2520, United States. kevin.strange@vanderbilt.edu
authors: Kevin
authors: K
authors: Strange
authors: Xiaohui
authors: X
authors: Yan
authors: Catherine
authors: C
authors: Lorin-Nebel
authors: Juan
authors: J
authors: Xing
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015220:Calcium Channels / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D020013:Calcium Signaling; D006066:Gonads / Q000502:physiology; D007422:Intestines / Q000502:physiology; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D000071740:ORAI1 Protein; D000071737:Stromal Interaction Molecule 1
chemical_list: D029742:Caenorhabditis elegans Proteins; D015220:Calcium Channels; D008565:Membrane Proteins; C519796:ORAI-1 protein, C elegans; D000071740:ORAI1 Protein; D000071737:Stromal Interaction Molecule 1; C516629:stim-1 protein, C elegans