ArticleThe Journal of biological chemistry2011
A cytosolic STIM2 preprotein created by signal peptide inefficiency activates ORAI1 in a store-independent manner.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- STIM-Orai signaling in neurons: integrating calcium dynamics and synaptic plasticity.Cell communication and signaling : CCS · 2026Review
- Alternatively spliced STIM2.3 is an evolutionarily late store-operated Ca2+ entry regulator expressed in brain.Journal of cell science · 2026Article
- New insights into the stromal interaction molecule 2 function and its impact on the immunomodulation of tumor microenvironment.Cell & bioscience · 2024Review
- STIM2 regulates NMDA receptor endocytosis that is induced by short-term NMDA receptor overactivation in cortical neurons.Cellular and molecular life sciences : CMLS · 2023Article
- STIM and Orai Mediated Regulation of Calcium Signaling in Age-Related Diseases.Frontiers in aging · 2022Review
- Computer-Based Drug Design of Positive Modulators of Store-Operated Calcium Channels to Prevent Synaptic Dysfunction in Alzheimer's Disease.International journal of molecular sciences · 2021Review
- STIM Proteins: An Ever-Expanding Family.International journal of molecular sciences · 2020Review
- Synergistic stabilization by nitrosoglutathione-induced thiol modifications in the stromal interaction molecule-2 luminal domain suppresses basal and store operated calcium entry.Scientific reports · 2020Article
- STIM2 (Stromal Interaction Molecule 2)-Mediated Increase in Resting Cytosolic Free CaHypertension (Dallas, Tex. : 1979) · 2018Article
- Molecular physiology and pathophysiology of stromal interaction molecules.Experimental biology and medicine (Maywood, N.J.) · 2018Review
- Constitutive calcium entry and cancer: updated views and insights.European biophysics journal : EBJ · 2017Review
- Role of STIM2 in cell function and physiopathology.The Journal of physiology · 2017Review
- STIMs and Orai1 regulate cytokine production in spinal astrocytes.Journal of neuroinflammation · 2016Article
- A STIM2 splice variant negatively regulates store-operated calcium entry.Nature communications · 2015Article
- Stim and Orai proteins in neuronal Ca(2+) signaling and excitability.Frontiers in cellular neuroscience · 2015Review
- Identification of steroid-sensitive gene-1/Ccdc80 as a JAK2-binding protein.Molecular endocrinology (Baltimore, Md.) · 2013Article
- Unraveling STIM2 function.Journal of physiology and biochemistry · 2012Review
- 2-APB-potentiated channels amplify CatSper-induced Ca(2+) signals in human sperm.The Biochemical journal · 2012Article
- ROS and SOCE: recent advances and controversies in the regulation of STIM and Orai.The Journal of physiology · 2012Review
- Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Calcium (Ca(2+)) influx through the plasma membrane store-operated Ca(2+) channel ORAI1 is controlled by Ca(2+) sensors of the stromal interaction molecule (STIM) family. STIM1 responds to endoplasmic reticulum (ER) Ca(2+) store depletion by redistributing and activating ORAI1 from regions of the ER juxtaposed to the plasma membrane. Unlike STIM1, STIM2 can regulate ORAI1 in a store-dependent and store-independent manner, but the mechanism by which this is achieved is unknown. Here we find that STIM2 is translated from a highly conserved methionine residue and is directed to the ER by an incredibly long 101-amino acid signal peptide. We find that although the majority of the total STIM2 population resides on the ER membrane, a second population escapes ER targeting to accumulate as a full-length preprotein in the cytosol, signal peptide intact. Unlike STIM2, preSTIM2 localizes to the inner leaflet of the plasma membrane where it interacts with ORAI1 to regulate basal Ca(2+) concentration and Ca(2+)-dependent gene transcription in a store-independent manner. Furthermore, a third protein comprising a fragment of the STIM2 signal peptide is released from the ER membrane into the cytosol where it regulates gene transcription in a Ca(2+)-independent manner. This study establishes a new model for STIM2-mediated regulation of ORAI1 in which two distinct proteins, STIM2 and preSTIM2, control store-dependent and store-independent modes of ORAI1 activation.
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Registered trials
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.