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CRAC channel activity in C. elegans is mediated by Orai1 and STIM1 homologues and is essential for ovulation and fertility.
J Physiol. 2007 Apr 01; 580(Pt 1):67-85.JP

Abstract

The Ca(2+) release-activated Ca(2+) (CRAC) channel is a plasma membrane Ca(2+) entry pathway activated by endoplasmic reticulum (ER) Ca(2+) store depletion. STIM1 proteins function as ER Ca(2+) sensors and regulate CRAC channel activation. Recent studies have demonstrated that CRAC channels are encoded by the human Orai1 gene and a homologous Drosophila gene. C. elegans intestinal cells express a store-operated Ca(2+) channel (SOCC) regulated by STIM-1. We cloned a full-length C. elegans cDNA that encodes a 293 amino acid protein, ORAI-1, homologous to human and Drosophila Orai1 proteins. ORAI-1 GFP reporters are co-expressed with STIM-1 in the gonad and intestine. Inositol 1,4,5-trisphosphate (IP(3))-dependent Ca(2+) signalling regulates C. elegans gonad function, fertility and rhythmic posterior body wall muscle contraction (pBoc) required for defecation. RNA interference (RNAi) silencing of orai-1 expression phenocopies stim-1 knockdown and causes sterility and prevents intestinal cell SOCC activation, but has no effect on pBoc or intestinal Ca(2+) signalling. Orai-1 RNAi suppresses pBoc defects induced by intestinal expression of a STIM-1 Ca(2+)-binding mutant, indicating that the proteins function in a common pathway. Co-expression of stim-1 and orai-1 cDNAs in HEK293 cells induces large inwardly rectifying cation currents activated by ER Ca(2+) depletion. The properties of this current recapitulate those of the native SOCC current. We conclude that C. elegans expresses bona fide CRAC channels that require the function of Orai1- and STIM1-related proteins. CRAC channels thus arose very early in animal evolution. In C. elegans, CRAC channels do not play obligate roles in all IP(3)-dependent signalling processes and ER Ca(2+) homeostasis. Instead, we suggest that CRAC channels carry out highly specialized and cell-specific signalling roles and that they may function as a failsafe mechanism to prevent Ca(2+) store depletion under pathophysiological and stress conditions.

Authors+Show Affiliations

Vanderbilt University Medical Center, T-4208 Medical Center North, Nashville, TN 37232-2520, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17218360

Citation

Lorin-Nebel, Catherine, et al. "CRAC Channel Activity in C. Elegans Is Mediated By Orai1 and STIM1 Homologues and Is Essential for Ovulation and Fertility." The Journal of Physiology, vol. 580, no. Pt 1, 2007, pp. 67-85.
Lorin-Nebel C, Xing J, Yan X, et al. CRAC channel activity in C. elegans is mediated by Orai1 and STIM1 homologues and is essential for ovulation and fertility. J Physiol. 2007;580(Pt 1):67-85.
Lorin-Nebel, C., Xing, J., Yan, X., & Strange, K. (2007). CRAC channel activity in C. elegans is mediated by Orai1 and STIM1 homologues and is essential for ovulation and fertility. The Journal of Physiology, 580(Pt 1), 67-85.
Lorin-Nebel C, et al. CRAC Channel Activity in C. Elegans Is Mediated By Orai1 and STIM1 Homologues and Is Essential for Ovulation and Fertility. J Physiol. 2007 Apr 1;580(Pt 1):67-85. PubMed PMID: 17218360.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CRAC channel activity in C. elegans is mediated by Orai1 and STIM1 homologues and is essential for ovulation and fertility. AU - Lorin-Nebel,Catherine, AU - Xing,Juan, AU - Yan,Xiaohui, AU - Strange,Kevin, Y1 - 2007/01/11/ PY - 2007/1/16/pubmed PY - 2007/5/30/medline PY - 2007/1/16/entrez SP - 67 EP - 85 JF - The Journal of physiology JO - J Physiol VL - 580 IS - Pt 1 N2 - The Ca(2+) release-activated Ca(2+) (CRAC) channel is a plasma membrane Ca(2+) entry pathway activated by endoplasmic reticulum (ER) Ca(2+) store depletion. STIM1 proteins function as ER Ca(2+) sensors and regulate CRAC channel activation. Recent studies have demonstrated that CRAC channels are encoded by the human Orai1 gene and a homologous Drosophila gene. C. elegans intestinal cells express a store-operated Ca(2+) channel (SOCC) regulated by STIM-1. We cloned a full-length C. elegans cDNA that encodes a 293 amino acid protein, ORAI-1, homologous to human and Drosophila Orai1 proteins. ORAI-1 GFP reporters are co-expressed with STIM-1 in the gonad and intestine. Inositol 1,4,5-trisphosphate (IP(3))-dependent Ca(2+) signalling regulates C. elegans gonad function, fertility and rhythmic posterior body wall muscle contraction (pBoc) required for defecation. RNA interference (RNAi) silencing of orai-1 expression phenocopies stim-1 knockdown and causes sterility and prevents intestinal cell SOCC activation, but has no effect on pBoc or intestinal Ca(2+) signalling. Orai-1 RNAi suppresses pBoc defects induced by intestinal expression of a STIM-1 Ca(2+)-binding mutant, indicating that the proteins function in a common pathway. Co-expression of stim-1 and orai-1 cDNAs in HEK293 cells induces large inwardly rectifying cation currents activated by ER Ca(2+) depletion. The properties of this current recapitulate those of the native SOCC current. We conclude that C. elegans expresses bona fide CRAC channels that require the function of Orai1- and STIM1-related proteins. CRAC channels thus arose very early in animal evolution. In C. elegans, CRAC channels do not play obligate roles in all IP(3)-dependent signalling processes and ER Ca(2+) homeostasis. Instead, we suggest that CRAC channels carry out highly specialized and cell-specific signalling roles and that they may function as a failsafe mechanism to prevent Ca(2+) store depletion under pathophysiological and stress conditions. SN - 0022-3751 UR - https://www.unboundmedicine.com/medline/citation/17218360/CRAC_channel_activity_in_C__elegans_is_mediated_by_Orai1_and_STIM1_homologues_and_is_essential_for_ovulation_and_fertility_ L2 - https://doi.org/10.1113/jphysiol.2006.124883 DB - PRIME DP - Unbound Medicine ER -