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Initial activation of STIM1, the regulator of store-operated calcium entry
Open accessAbstract
Physiological Ca2+ signaling in T lymphocytes and other cells depends on the STIM-ORAI pathway of store-operated Ca2+ entry. STIM1 and STIM2 are Ca2+ sensors in the endoplasmic reticulum (ER) membrane, with ER-luminal domains that monitor cellular Ca2+ stores and cytoplasmic domains that gate ORAI channels in the plasma membrane. The STIM ER-luminal domain dimerizes or oligomerizes upon dissociation of Ca2+, but the mechanism transmitting activation to the STIM cytoplasmic domain was previously undefined. Using Tb3+-acceptor energy transfer, we show that dimerization of STIM1 ER-luminal domains causes an extensive conformational change in mouse STIM1 cytoplasmic domains. The conformational change, triggered by apposition of the predicted coiled-coil 1 (CC1) regions, releases the ORAI-activating domains from their interaction with the CC1 regions and allows physical extension of the STIM1 cytoplasmic domain across the gap between ER and plasma membrane and communication with ORAI channels.
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Store-Operated Calcium Channels
Parekh, A. B., & Putney, J. W. (2005) · Physiological Reviews · doi:10.1152/physrev.00057.2003 · Cited by 2,089
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Prakriya, M., & Lewis, R. S. (2015) · Physiological Reviews · doi:10.1152/physrev.00020.2014 · Cited by 1,239
Diseases caused by mutations in ORAI1 and STIM1
Lacruz, R. S., & Feske, S. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12938 · Cited by 443
GRAM domain proteins specialize functionally distinct ER-PM contact sites in human cells
Besprozvannaya, M., Dickson, E., Li, H., Ginburg, K. S., Bers, D. M., Auwerx, J., & Nunnari, J. (2018) · eLife · doi:10.7554/elife.31019 · Cited by 128
Chen, C.-H., Di, Y.-Q., Shen, Q.-Y., Wang, J.-X., & Zhao, X.-F. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.008484 · Cited by 16
Is hydrogen ion (H+) the real second messenger in calcium signalling?
Molinari, G. (2015) · Cellular Signalling · doi:10.1016/j.cellsig.2015.03.023 · Cited by 13
Metadata
- Authors
- Zhou, Y., Srinivasan, P., Razavi, S., Seymour, S., Meraner, P., Gudlur, A., Stathopulos, P. B., Ikura, M., Rao, A., & Hogan, P. G.
- Venue
- Nature Structural & Molecular Biology
- Published
- 2013-07-14
- Volume
- 20
- Issue
- 8
- Pages
- 973-981
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- OpenAlex
- W1989178712
- Cited by
- 212
- References
- 1
- FWCI
- 9.61
- Type
- journal article
- Language
- en
- Open access
- green
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- Zhou, Y., Srinivasan, P., Razavi, S., Seymour, S., Meraner, P., Gudlur, A., Stathopulos, P. B., Ikura, M., Rao, A., & Hogan, P. G. (2013). Initial activation of STIM1, the regulator of store-operated calcium entry. Nature Structural & Molecular Biology. https://doi.org/10.1038/nsmb.2625
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