ArticleChannels (Austin, Tex.)
A plasma membrane-targeted cytosolic domain of STIM1 selectively activates ARC channels, an arachidonate-regulated store-independent Orai channel.
Article in Channels (Austin, Tex.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 32 citations in OpenAlex.
- STIM1-mediated calcium influx controls antifungal immunity and the metabolic function of non-pathogenic Th17 cells.EMBO molecular medicine · 2020Article
- Ion Channels in Pulmonary Hypertension: A Therapeutic Interest?International journal of molecular sciences · 2018Review
- Phosphorylation-mediated structural changes within the SOAR domain of stromal interaction molecule 1 enable specific activation of distinct Orai channels.The Journal of biological chemistry · 2018Article
- ORAI Calcium Channels.Physiology (Bethesda, Md.) · 2017Review
- Selective activation of distinct Orai channels by STIM1.Cell calcium · 2017Review
- Orai1, 2, 3 and STIM1 promote store-operated calcium entry in pulmonary arterial smooth muscle cells.Cell death discovery · 2017Article
- Orai channel-mediated Ca2+ signals in vascular and airway smooth muscle.American journal of physiology. Cell physiology · 2016Review
- Orai3 Surface Accumulation and Calcium Entry Evoked by Vascular Endothelial Growth Factor.Arteriosclerosis, thrombosis, and vascular biology · 2015Article
- Anchoring protein AKAP79-mediated PKA phosphorylation of STIM1 determines selective activation of the ARC channel, a store-independent Orai channel.The Journal of physiology · 2015Article
- Arachidonate-regulated Ca(2+) influx in human airway smooth muscle.American journal of respiratory cell and molecular biology · 2014Article
- Members of the thrombospondin gene family bind stromal interaction molecule 1 and regulate calcium channel activity.Matrix biology : journal of the International Society for Matrix Biology · 2014Article
- Complex role of STIM1 in the activation of store-independent Orai1/3 channels.The Journal of general physiology · 2014Article
- Mechanisms of STIM1 activation of store-independent leukotriene C4-regulated Ca2+ channels.Molecular and cellular biology · 2013Article
- STIM1/Orai1-mediated SOCE: current perspectives and potential roles in cardiac function and pathology.American journal of physiology. Heart and circulatory physiology · 2013Review
- Molecular basis of activation of the arachidonate-regulated Ca2+ (ARC) channel, a store-independent Orai channel, by plasma membrane STIM1.The Journal of physiology · 2013Article
- Emerging roles of Orai3 in pathophysiology.Channels (Austin, Tex.)Review
- Exploring the unique features of the ARC channel, a store-independent Orai channel.Channels (Austin, Tex.)Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The Orai family of calcium channels includes the store-operated CRAC channels and store-independent, arachidonic acid (AA)-regulated ARC channels. Both depend on STIM1 for their activation but, whereas CRAC channel activation involves sensing the depletion of intracellular calcium stores via a luminal N terminal EF-hand of STIM1 in the endoplasmic reticulum (ER) membrane, ARC channels are exclusively activated by the pool of STIM1 that constitutively resides in the plasma membrane (PM). Here, the EF-hand is extracellular and unlikely to ever lose its bound calcium, suggesting that STIM1-dependent activation of ARC channels is very different from that of CRAC channels. We now show that attachment of the cytosolic portion of STIM1 to the inner face of the PM via an N terminal Lck-domain sequence is sufficient to enable normal AA-dependent activation of ARC channels, while failing to allow activation of store-operated CRAC channels. Introduction of a point mutation within the Lck-domain resulted in the loss of both PM localization and ARC channel activation. Reversing the orientation of the PM-anchored STIM1 C terminus via a C-terminal CAAX-box fails to support either CRAC or ARC channel activation. Finally, the Lck-anchored STIM1 C-terminal domain also enabled the exclusive activation of the ARC channels following physiological agonist addition. These data demonstrate that simple tethering of the cytosolic C-terminal domain of STIM1 to the inner face of the PM is sufficient to allow the full, normal and exclusive activation of ARC channels, and that the N-terminal regions of STIM1 (including the EF-hand domain) play no significant role in this activation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.