ArticleMolecular biology of the cell2016
α-SNAP regulates dynamic, on-site assembly and calcium selectivity of Orai1 channels.
Article in Molecular biology of the cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Syntaxin11 Deficiency Inhibits CRAC Channel Priming To Suppress Cytotoxicity And Gene Expression In FHLH4 Patient T Lymphocytes.bioRxiv : the preprint server for biology · 2024Article
- Single-Molecule Imaging Reveals Differential AT1R Stoichiometry Change in Biased Signaling.International journal of molecular sciences · 2023Article
- Alpha-SNAP (M105I) mutation promotes neuronal differentiation of neural stem/progenitor cells through overactivation of AMPK.Frontiers in cell and developmental biology · 2023Article
- Highlighting the Multifaceted Role of Orai1 N-Terminal- and Loop Regions for Proper CRAC Channel Functions.Cells · 2022Review
- More Than Just Simple Interaction between STIM and Orai Proteins: CRAC Channel Function Enabled by a Network of Interactions with Regulatory Proteins.International journal of molecular sciences · 2021Review
- Article
- Proteins Interacting with STIM1 and Store-Operated CaProgress in molecular and subcellular biology · 2021Review
- Determining the correct stoichiometry of Kv2.1/Kv6.4 heterotetramers, functional in multiple stoichiometrical configurations.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Pleiotropic effects of alpha-SNAP M105I mutation on oocyte biology: ultrastructural and cellular changes that adversely affect female fertility in mice.Scientific reports · 2019Article
- Mining of Ebola virus entry inhibitors identifies approved drugs as two-pore channel pore blockers.Biochimica et biophysica acta. Molecular cell research · 2019Article
- Numbers count: How STIM and Orai stoichiometry affect store-operated calcium entry.Cell calcium · 2019Review
- Multiple paralogues of α-SNAP in Giardia lamblia exhibit independent subcellular localization and redistribution during encystation and stress.Parasites & vectors · 2018Article
- ER-plasma membrane junctions: Why and how do we study them?Biochimica et biophysica acta. Molecular cell research · 2017Review
- NaeLife · 2017Article
- Store-Operated CaCurrent molecular biology reports · 2017Review
- Immunological Disorders: Regulation of CaAdvances in experimental medicine and biology · 2017Review
- The Orai1 Store-operated Calcium Channel Functions as a Hexamer.The Journal of biological chemistry · 2016Article
- Functional Analysis of Orai1 Concatemers Supports a Hexameric Stoichiometry for the CRAC Channel.Biophysical journal · 2016Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Orai1 forms a highly calcium-selective pore of the calcium release activated channel, and α-SNAP is necessary for its function. Here we show that α-SNAP regulates on-site assembly of Orai1 dimers into calcium-selective multimers. We find that Orai1 is a dimer in resting primary mouse embryonic fibroblasts but displays variable stoichiometry in the plasma membrane of store-depleted cells. Remarkably, α-SNAP depletion induces formation of higher-order Orai1 oligomers, which permeate significant levels of sodium via Orai1 channels. Sodium permeation in α-SNAP-deficient cells cannot be corrected by tethering multiple Stim1 domains to Orai1 C-terminal tail, demonstrating that α-SNAP regulates functional assembly and calcium selectivity of Orai1 multimers independently of Stim1 levels. Fluorescence nanoscopy reveals sustained coassociation of α-SNAP with Stim1 and Orai1, and α-SNAP-depleted cells show faster and less constrained mobility of Orai1 within ER-PM junctions, suggesting Orai1 and Stim1 coentrapment without stable contacts. Furthermore, α-SNAP depletion significantly reduces fluorescence resonance energy transfer between Stim1 and Orai1 N-terminus but not C-terminus. Taken together, these data reveal a unique role of α-SNAP in the on-site functional assembly of Orai1 subunits and suggest that this process may, in part, involve enabling crucial low-affinity interactions between Orai1 N-terminus and Stim1.
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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.