Biophysical characterization of the EF-hand and SAM domain containing Ca2+ sensory region of STIM1 and STIM2

Zheng, Lirong; Stathopulos, Peter B.; Li, Guangyao; Ikura, Mitsuhiko

doi:10.1016/j.bbrc.2007.12.129

Cited by 133 publications

(129 citation statements)

References 30 publications

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“…A lower Ca 2ϩ -activation threshold of STIM2 as compared with STIM1 has been suggested (2), although N-terminal Ca 2ϩ -binding affinity seems to be similar for STIM1 and STIM2 (27)(28)(29). In STIM2 knock-out mice, and also in several cell types in which STIM2 has been silenced, SOCE amplitude is only slightly reduced.…”

Section: Stim1 and Stim2 Are Endoplasmic Reticulum (Er)mentioning

confidence: 99%

Human Muscle Economy Myoblast Differentiation and Excitation-Contraction Coupling Use the Same Molecular Partners, STIM1 and STIM2

Darbellay

Arnaudeau

Ceroni

et al. 2010

Journal of Biological Chemistry

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Our recent work identified store-operated Ca 2؉ entry (SOCE) as the critical Ca 2؉ source required for the induction of human myoblast differentiation (Darbellay, B., Arnaudeau, S., König, S., Jousset, H., Bader, C., Demaurex, N., and Bernheim, L. (2009) J. Biol. Chem. 284, 5370 -5380). The present work indicates that STIM2 silencing, similar to STIM1 silencing, reduces myoblast SOCE amplitude and differentiation. Because myoblasts in culture can be induced to differentiate into myotubes, which spontaneously contract in culture, we used the same molecular tools to explore whether the Ca 2؉ mechanism of excitation-contraction coupling also relies on STIM1 and STIM2. Live cell imaging of early differentiating myoblasts revealed a characteristic clustering of activated STIM1 and STIM2 during the first few hours of differentiation. Thapsigargin-induced depletion of endoplasmic reticulum Ca 2؉ content caused STIM1 and STIM2 redistribution into clusters, and co-localization of both STIM proteins. Interaction of STIM1 and STIM2 was revealed by a rapid increase in fluorescence resonance energy transfer between CFP-STIM1 and YFP-STIM2 after SOCE activation and confirmed by co-immunoprecipitation of endogenous STIM1 and STIM2. Although both STIM proteins clearly contribute to SOCE and are required during the differentiation process, STIM1 and STIM2 are functionally largely redundant as overexpression of either STIM1 or STIM2 corrected most of the impact of STIM2 or STIM1 silencing on SOCE and differentiation. With respect to excitation-contraction, we observed that human myotubes rely also on STIM1 and STIM2 to refill their endoplasmic reticulum Ca 2؉ -content during repeated KCl-induced Ca 2؉ releases. This indicates that STIM2 is a necessary partner of STIM1 for excitation-contraction coupling. Thus, both STIM proteins are required and interact to control SOCE during human myoblast differentiation and human myotube excitationcontraction coupling. STIM1 and STIM2 are endoplasmic reticulum (ER)2 transmembrane proteins that are activated by a drop in Ca 2ϩ content in the ER (2-5). Once activated, STIM1 and STIM2 trigger a Ca 2ϩ influx (also called store-operated Ca 2ϩ entry (SOCE)) through Ca 2ϩ -selective Orai channels located at the plasma membrane (6 -13). This Ca 2ϩ influx restores the ER Ca 2ϩ content (2-4, 10, 12, 14 -26).Several studies examined whether STIM2 had a specific role, distinct from STIM1, but no clear answer has emerged yet. A lower Ca 2ϩ -activation threshold of STIM2 as compared with STIM1 has been suggested (2), although N-terminal Ca 2ϩ -binding affinity seems to be similar for STIM1 and STIM2 (27-29). In STIM2 knock-out mice, and also in several cell types in which STIM2 has been silenced, SOCE amplitude is only slightly reduced. This could reflect either a smaller activation of Orai1 by the N-terminal part of STIM2 or a lower expression of STIM2 as compared with STIM1 (3,4,24,30). In other studies, overexpression of STIM2 has been reported to inhibit SOCE (31) or, on the contrary, to restore SOCE i...

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Section: Stim1 and Stim2 Are Endoplasmic Reticulum (Er)mentioning

confidence: 99%

Human Muscle Economy Myoblast Differentiation and Excitation-Contraction Coupling Use the Same Molecular Partners, STIM1 and STIM2

Darbellay

Arnaudeau

Ceroni

et al. 2010

Journal of Biological Chemistry

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“…The propensity of STIM1 to aggregate when its EF-hands are not bound by Ca 2+ can be demonstrated using just a short recombinant N-terminal fragment of STIM1, containing only the EF-hands and the adjacent SAM (sterile α-motif) domain [56,57]. Once formed, the STIM1 clusters preferentially localize to sites of ER-plasma membrane apposition and colocalize partially with clusters of ORAI1 [55,58, [61,62].…”

Section: Gating Of Crac Channels By Local Aggregation Of Stim and Oraimentioning

confidence: 99%

Calcium signaling in lymphocytes

Oh‐hora¹,

Rao²

2008

Current Opinion in Immunology

352

270

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In cells of the immune system, calcium signals are essential for diverse cellular functions including differentiation, effector function and gene transcription. After engagement of immunoreceptors such as T-cell and B-cell antigen receptors and the Fc receptors on mast cells and NK cells, the intracellular concentration of calcium ions is increased through the sequential operation of two interdependent processes: depletion of endoplasmic reticulum Ca 2+ stores as a result of binding of inositol trisphosphate (IP 3 ) to IP 3 receptors, followed by "store-operated" Ca 2+ entry through plasma membrane Ca 2+ channels. In lymphocytes, mast cells and other immune cell types, store-operated Ca 2+ entry through specialised Ca 2+ release-activated calcium (CRAC) channels constitutes the major pathway of intracellular Ca 2+ increase. A recent breakthrough in our understanding of CRAC channel function is the identification of STIM and ORAI, two essential regulators of CRAC channel function. This review focuses on the signaling pathways upstream and downstream of Ca 2+ influx (the STIM/ ORAI and calcineurin/ NFAT pathways respectively).

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“…These rearrangements expose the C-terminal polybasic domain, which interacts with phosphatidylinositol 4,5-bisphosphate in the plasma membrane (PM) and drives STIM accumulation at ER-PM junctions (Wu et al, 2006;Liou et al, 2007;Ercan et al, 2009;Park et al, 2009). Although STIM1 and STIM2 respond similarly to store depletion, STIM2 differs from STIM1 in being partially localized at ER-PM junctions even in store-replete cells, likely as a result of its lower affinity for ER Ca 2+ relative to STIM1 (Brandman et al, 2007;Zheng et al, 2008). At ER-PM junctions STIM proteins directly bind to and trap Orai channels (Park et al, 2009;Wu et al, 2014) through their CRAC activation domains (CADs; also known as SOAR [STIM1 Orai1 activation region] or CCb9; Kawasaki et al, 2009;Park et al, 2009;Yuan et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Alternative splicing converts STIM2 from an activator to an inhibitor of store-operated calcium channels

Rana¹,

Yen²,

Sadaghiani³

et al. 2015

J Gen Physiol

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Biophysical characterization of the EF-hand and SAM domain containing Ca2+ sensory region of STIM1 and STIM2

Cited by 133 publications

References 30 publications

Human Muscle Economy Myoblast Differentiation and Excitation-Contraction Coupling Use the Same Molecular Partners, STIM1 and STIM2

Human Muscle Economy Myoblast Differentiation and Excitation-Contraction Coupling Use the Same Molecular Partners, STIM1 and STIM2

Calcium signaling in lymphocytes

Alternative splicing converts STIM2 from an activator to an inhibitor of store-operated calcium channels

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