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Role of STIM and Orai proteins in the store-operated calcium signaling pathway.
Cell Calcium. 2007 Aug; 42(2):173-82.CC

Abstract

Ca(2+) signals are universal among cells in regulating a spectrum of cellular responses. Phospholipase C-coupled receptors activate two components of Ca(2+) signals--rapid Ca(2+) release from ER stores, followed by slower Ca(2+) entry from outside the cell. The coupling process between ER and PM to mediate this "store-operated" Ca(2+) entry process remained until recently a molecular mystery. The recent discovery of the necessity for STIM1 and Orai proteins in this process has provided crucial information on the coupling mechanism between stores and PM Ca(2+) entry. STIM1 is a single spanning membrane protein with an unpaired Ca(2+) binding EF-hand and appears to function as the sensor of ER luminal Ca(2+), and, through redistribution in the ER, transduces information directly to the PM. Orai1 is a tetra-spanning PM protein and functions as the highly Ca(2+)-selective channel in the PM that is gated through interactions with the store-activated ER Ca(2+) sensor. Recent evidence shows the two proteins together are necessary and sufficient for the function of store-operated Ca(2+) entry. However, many questions arise about how and where the interactions of the STIM1 and Orai1 proteins occur within cells. Here we discuss recent information and ideas about the coupling between these proteins that leads to store-operated channel activation.

Authors+Show Affiliations

Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 North Greene Street, Baltimore, MD 21201, United States.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

17602740

Citation

Hewavitharana, Thamara, et al. "Role of STIM and Orai Proteins in the Store-operated Calcium Signaling Pathway." Cell Calcium, vol. 42, no. 2, 2007, pp. 173-82.
Hewavitharana T, Deng X, Soboloff J, et al. Role of STIM and Orai proteins in the store-operated calcium signaling pathway. Cell Calcium. 2007;42(2):173-82.
Hewavitharana, T., Deng, X., Soboloff, J., & Gill, D. L. (2007). Role of STIM and Orai proteins in the store-operated calcium signaling pathway. Cell Calcium, 42(2), 173-82.
Hewavitharana T, et al. Role of STIM and Orai Proteins in the Store-operated Calcium Signaling Pathway. Cell Calcium. 2007;42(2):173-82. PubMed PMID: 17602740.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of STIM and Orai proteins in the store-operated calcium signaling pathway. AU - Hewavitharana,Thamara, AU - Deng,Xiaoxiang, AU - Soboloff,Jonathan, AU - Gill,Donald L, Y1 - 2007/06/28/ PY - 2007/03/02/received PY - 2007/03/22/revised PY - 2007/03/23/accepted PY - 2007/7/3/pubmed PY - 2007/9/29/medline PY - 2007/7/3/entrez SP - 173 EP - 82 JF - Cell calcium JO - Cell Calcium VL - 42 IS - 2 N2 - Ca(2+) signals are universal among cells in regulating a spectrum of cellular responses. Phospholipase C-coupled receptors activate two components of Ca(2+) signals--rapid Ca(2+) release from ER stores, followed by slower Ca(2+) entry from outside the cell. The coupling process between ER and PM to mediate this "store-operated" Ca(2+) entry process remained until recently a molecular mystery. The recent discovery of the necessity for STIM1 and Orai proteins in this process has provided crucial information on the coupling mechanism between stores and PM Ca(2+) entry. STIM1 is a single spanning membrane protein with an unpaired Ca(2+) binding EF-hand and appears to function as the sensor of ER luminal Ca(2+), and, through redistribution in the ER, transduces information directly to the PM. Orai1 is a tetra-spanning PM protein and functions as the highly Ca(2+)-selective channel in the PM that is gated through interactions with the store-activated ER Ca(2+) sensor. Recent evidence shows the two proteins together are necessary and sufficient for the function of store-operated Ca(2+) entry. However, many questions arise about how and where the interactions of the STIM1 and Orai1 proteins occur within cells. Here we discuss recent information and ideas about the coupling between these proteins that leads to store-operated channel activation. SN - 0143-4160 UR - https://www.unboundmedicine.com/medline/citation/17602740/Role_of_STIM_and_Orai_proteins_in_the_store_operated_calcium_signaling_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0143-4160(07)00078-4 DB - PRIME DP - Unbound Medicine ER -