The DOI matches its Crossref record; 20 of the 20 references it cites were found in a registry or an index.
Orai1 and STIM Reconstitute Store-operated Calcium Channel Function
Open accessAbstract
The two membrane proteins, STIM1 and Orai1, have each been shown to be essential for the activation of store-operated channels (SOC). Yet, how these proteins functionally interact is not known. Here, we reveal that STIM1 and Orai1 expressed together reconstitute functional SOCs. Expressed alone, Orai1 strongly reduces store-operated Ca(2+) entry (SOCE) in human embryonic kidney 293 cells and the Ca(2+) release-activated Ca(2+) current (I(CRAC)) in rat basophilic leukemia cells. However, expressed along with the store-sensing STIM1 protein, Orai1 causes a massive increase in SOCE, enhancing the rate of Ca(2+)entry by up to 103-fold. This entry is entirely store-dependent since the same coexpression causes no measurable store-independent Ca(2+) entry. The entry is completely blocked by the SOC blocker, 2-aminoethoxydiphenylborate. Orai1 and STIM1 coexpression also caused a large gain in CRAC channel function in rat basophilic leukemia cells. The close STIM1 homologue, STIM2, inhibited SOCE when expressed alone but coexpressed with Orai1 caused substantial constitutive (store-independent) Ca(2+) entry. STIM proteins are known to mediate Ca(2+) store-sensing and endoplasmic reticulum-plasma membrane coupling with no intrinsic channel properties. Our results revealing a powerful gain in SOC function dependent on the presence of both Orai1 and STIM1 strongly suggest that Orai1 contributes the PM channel component responsible for Ca(2+) entry. The suppression of SOC function by Orai1 overexpression likely reflects a required stoichiometry between STIM1 and Orai1.
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Cites
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Cited by
Store-Operated Calcium Channels
Parekh, A. B., & Putney, J. W. (2005) · Physiological Reviews · doi:10.1152/physrev.00057.2003 · Cited by 2,089
Calcium signalling in lymphocyte activation and disease
Feske, S. (2007) · Nature Reviews Immunology · doi:10.1038/nri2152 · Cited by 1,043
Molecular Basis of Calcium Signaling in Lymphocytes: STIM and ORAI
Hogan, P. G., Lewis, R. S., & Rao, A. (2010) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132550 · Cited by 760
Sadana, R., & Dessauer, C. W. (2009) · Neurosignals · doi:10.1159/000166277 · Cited by 361
Altered calcium signaling in cancer cells
Stewart, T. A., Yapa, K. T. D. S., & Monteith, G. R. (2015) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2014.08.016 · Cited by 337
Metadata
- Authors
- Soboloff, J., Spassova, M. A., Tang, X. D., Hewavitharana, T., Xu, W., & Gill, D. L.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2006-07
- Volume
- 281
- Issue
- 30
- Pages
- 20661-20665
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2012471725
- Cited by
- 549
- References
- 20
- FWCI
- 25.59
- Type
- journal article
- Language
- en
- Open access
- hybrid
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