ArticleThe Journal of cell biology2022
TRPC3 channel gating by lipids requires localization at the ER/PM junctions defined by STIM1.
Article in The Journal of cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- The role of IPPflugers Archiv : European journal of physiology · 2026Review
- Review
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- A steady-state pool of calcium-dependent actin is maintained by Homer and controls epithelial mechanosensation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Moderately severe osteogenesis imperfecta-like osteochondrodysplasia associated with heterozygous variants in bothJBMR plus · 2025Article
- Utilizing native nanodiscs to isolate active TRPC3 channels and expand structural analysis capabilities.Scientific reports · 2025Article
- Lipid transporters E-Syt3 and ORP5 regulate epithelial ion transport by controlling phosphatidylserine enrichment at ER/PM junctions.The EMBO journal · 2025Article
- Multiple cAMP/PKA complexes at the STIM1 ER/PM junction specified by E-Syt1 and E-Syt2 reciprocally gates ANO1 (TMEM16A) via CaNature communications · 2025Article
- Pathophysiological significance and modulation of the transient receptor potential canonical 3 ion channel.Medicinal research reviews · 2024Review
- Thermosensing ability of TRPC5: current knowledge and unsettled questions.The journal of physiological sciences : JPS · 2024Review
- PACS-1 Interacts with TRPC3 and ESyt1 to Mediate Protein Trafficking while Promoting SOCE and Cooperatively Regulating Hormone Secretion.ACS omega · 2024Article
- PIPNature communications · 2024Article
- Non-canonical helical transitions and conformational switching are associated with characteristic flexibility and disorder indices in TRP and Kv channels.Channels (Austin, Tex.) · 2023Article
- Review
- PtdSer as a signaling lipid determined by privileged localization of ORP5 and ORP8 at ER/PM junctional foci to determine PM and ER PtdSer/PI(4)P ratio and cell function.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Diacylglycerol Activates theInternational journal of molecular sciences · 2023Article
- Hydrophobic interactions within the C terminus pole helices tunnel regulate calcium-dependent inactivation of TRPC3 in a calmodulin-dependent manner.Cell calcium · 2023Article
- The sun, cholesterol and Orai1 conspire in melanoma.The EMBO journal · 2022Article
- TRPC channels as emerging targets for seizure disorders.Trends in pharmacological sciences · 2022Review
- TRPV6 Regulation by Cis-22a and Cholesterol.Biomolecules · 2022Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
TRPC3, a member of the transient receptor potential (TRP) superfamily of cation channels, is a lipid-regulated, Ca2+-permeable channel that mediates essential components of the receptor evoked Ca2+ signal. The modes and mechanisms by which lipids regulate TRPC3 and other members of the TRPC channel family are not well understood. Here, we report that PI(4,5)P2 regulates TRPC3 in three independent modes. PLC-dependent hydrolysis generates diacylglycerol (DAG) that interacts with lipid-binding site 2 in the channel pore. PI(4,5)P2 interacts with lipid site 1 to inhibit TRPC3 opening and regulate access of DAG to the pore lipid site 2. PI(4,5)P2 is required for regulating pore ionic selectivity by receptor stimulation. Notably, the activation and regulation of TRPC3 by PI(4,5)P2 require recruitment of TRPC3 to the ER/PM junctions at a PI(4,5)P2-rich domain. Accordingly, we identified an FFAT site at the TRPC3 N-terminal loop within the linker helices that envelope the C-terminus pole helix. The FFAT site interacts with the ER-resident VAPB to recruit TRPC3 to the ER/PM junctions and control its receptor-mediated activation. The TRPC3's lipid interacting sites are fully conserved in TRPC6 and TRPC7 and in part in other TRPC channels. These findings inform on multiple modes of regulation of ion channels by lipids that may be relevant to diseases affected by aberrant TRPC channel functions.
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