Distinct gating mechanism of SOC channel involving STIM-Orai coupling and an intramolecular interaction of Orai in Caenorhabditis elegans

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Title
Distinct gating mechanism of SOC channel involving STIM-Orai coupling and an intramolecular interaction of Orai in Caenorhabditis elegans
Author(s)
K M Kim; T Wijerathne; J H Hur; U J Kang; I H Kim; Y C Kweon; A R Lee; S J Jeong; S K Lee; Y Y Lee; Bo Woong SimJong Hee Lee; C Baig; Sun-Uk Kim; Kyu Tae Chang; K P Lee; C Y Park
Bibliographic Citation
Proceedings of National Academy of Sciences of United States of America, vol. 115, no. 20, pp. e4623-e4632
Publication Year
2018
Abstract
Store-operated calcium entry (SOCE), an important mechanism of Ca2+ signaling in a wide range of cell types, is mediated by stromal interaction molecule (STIM), which senses the depletion of endoplasmic reticulum Ca2+ stores and binds and activates Orai channels in the plasma membrane. This inside-out mechanism of Ca2+ signaling raises an interesting question about the evolution of SOCE: How did these two proteins existing in different cellular compartments evolve to interact with each other? We investigated the gating mechanism of Caenorhabditis elegans Orai channels. Our analysis revealed a mechanism of Orai gating by STIM binding to the intracellular 2-3 loop of Orai in C. elegans that is radically different from Orai gating by STIM binding to the N and C termini of Orai in mammals. In addition, we found that the conserved hydrophobic amino acids in the 2-3 loop of Orai1 are important for the oligomerization and gating of channels and are regulated via an intramolecular interaction mechanism mediated by the N and C termini of Orai1. This study identifies a previously unknown SOCE mechanism in C. elegans and suggests that, while the STIM?Orai interaction is conserved between invertebrates and mammals, the gating mechanism for Orai channels differs considerably.
Keyword
Ca2+ signalingCaenorhabditis elegansOrai1SOCESTIM1
ISSN
0027-8424
Publisher
Natl Acad Sciences
DOI
http://dx.doi.org/10.1073/pnas.1714986115
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of Bioinfrastructure > Futuristic Animal Resource & Research Center > 1. Journal Articles
Ochang Branch Institute > Division of Bioinfrastructure > National Primate Research Center > 1. Journal Articles
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