ArticleThe Journal of biological chemistry2014
Molecular determinants mediating gating of Transient Receptor Potential Canonical (TRPC) channels by stromal interaction molecule 1 (STIM1).
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 92 citations in OpenAlex.
- Review
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- STIM Proteins: The Gas and Brake of Calcium Entry in Neurons.Neuroscience bulletin · 2025Review
- The spiny relationship between parallel fibers, climbing fibers, and Purkinje cells.Frontiers in physiology · 2025Review
- Thermosensing ability of TRPC5: current knowledge and unsettled questions.The journal of physiological sciences : JPS · 2024Review
- Neuronal Nitric Oxide Synthase Regulates Cerebellar Parallel Fiber Slow EPSC in Purkinje Neurons by Modulating STIM1-Gated TRPC3-Containing Channels.Cerebellum (London, England) · 2024Article
- Roles of TRP and PIEZO receptors in autoimmune diseases.Expert reviews in molecular medicine · 2024Review
- Regulatory mechanisms controlling store-operated calcium entry.Frontiers in physiology · 2023Review
- Hydrophobic interactions within the C terminus pole helices tunnel regulate calcium-dependent inactivation of TRPC3 in a calmodulin-dependent manner.Cell calcium · 2023Article
- Salivary gland function, development, and regeneration.Physiological reviews · 2022Review
- TRPC3 channel gating by lipids requires localization at the ER/PM junctions defined by STIM1.The Journal of cell biology · 2022Article
- Review
- TRP Channels as Molecular Targets to Relieve Endocrine-Related Diseases.Frontiers in molecular biosciences · 2022Review
- Endoplasmic Reticulum-Plasma Membrane Contact Sites as an Organizing Principle for Compartmentalized Calcium and cAMP Signaling.International journal of molecular sciences · 2021Review
- Proteins Interacting with STIM1 and Store-Operated CaProgress in molecular and subcellular biology · 2021Review
- Store-Operated Calcium Entry in the Cardiovascular System.Advances in experimental medicine and biology · 2021Review
- Obligatory role for PKCδ in PIPThe Journal of physiology · 2020Article
- TRPC channels: Structure, function, regulation and recent advances in small molecular probes.Pharmacology & therapeutics · 2020Review
- Review
- Insights into Activation Mechanisms of Store-Operated TRPC1 Channels in Vascular Smooth Muscle.Cells · 2020Review
Corrections and comments
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Authors and funding
10 authors at 8 institutions in 2 countries.
Funding
Abstract
Transient receptor potential canonical (TRPC) channels mediate a critical part of the receptor-evoked Ca(2+) influx. TRPCs are gated open by the endoplasmic reticulum Ca(2+) sensor STIM1. Here we asked which stromal interaction molecule 1 (STIM1) and TRPC domains mediate the interaction between them and how this interaction is used to open the channels. We report that the STIM1 Orai1-activating region domain of STIM1 interacts with the TRPC channel coiled coil domains (CCDs) and that this interaction is essential for opening the channels by STIM1. Thus, disruption of the N-terminal (NT) CCDs by triple mutations eliminated TRPC surface localization and reduced binding of STIM1 to TRPC1 and TRPC5 while increasing binding to TRPC3 and TRPC6. Single mutations in TRPC1 NT or C-terminal (CT) CCDs reduced interaction and activation of TRPC1 by STIM1. Remarkably, single mutations in the TRPC3 NT CCD enhanced interaction and regulation by STIM1. Disruption in the TRPC3 CT CCD eliminated regulation by STIM1 and the enhanced interaction caused by NT CCD mutations. The NT CCD mutations converted TRPC3 from a TRPC1-dependent to a TRPC1-independent, STIM1-regulated channel. TRPC1 reduced the FRET between BFP-TRPC3 and TRPC3-YFP and between CFP-TRPC3-YFP upon stimulation. Accordingly, knockdown of TRPC1 made TRPC3 STIM1-independent. STIM1 dependence of TRPC3 was reconstituted by the TRPC1 CT CCD alone. Knockout of Trpc1 and Trpc3 similarly inhibited Ca(2+) influx, and inhibition of Trpc3 had no further effect on Ca(2+) influx in Trpc1(-/-) cells. Cell stimulation enhanced the formation of Trpc1-Stim1-Trpc3 complexes. These findings support a model in which the TRPC3 NT and CT CCDs interact to shield the CT CCD from interaction with STIM1. The TRPC1 CT CCD dissociates this interaction to allow the STIM1 Orai1-activating region within STIM1 access to the TRPC3 CT CCD and regulation of TRPC3 by STIM1. These studies provide evidence that the TRPC channel CCDs participate in channel gating.
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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.