TRPC1: a core component of store-operated calcium channels
1Building 10, Room 1N-113, Secretory Physiology Section, GTTB (Gene Therapy and Therapeutics Branch), NIDCR (National Institute of Dental And Craniofacial Research), NIH (National Institutes of Health), Bethesda, MD 20892, USA. indu.ambudkar@nih.gov
Abstract:
The TRPC (transient receptor potential canonical) proteins are activated in response to agonist-stimulated PIP(2) (phosphatidylinositol 4,5-bisphosphate) hydrolysis and have been suggested as candidate components of the elusive SOC (store-operated calcium channel). TRPC1 is currently the strongest candidate component of SOC. Endogenous TRPC1 has been shown to contribute to SOCE (store-operated calcium entry) in several different cell types. However, the mechanisms involved in the regulation of TRPC1 and its exact physiological function have yet to be established. Studies from our laboratory and several others have demonstrated that TRPC1 is assembled in a signalling complex with key calcium signalling proteins in functionally specific plasma membrane microdomains. Furthermore, critical interactions between TRPC1 monomers as well as interactions between TRPC1 and other proteins determine the surface expression and function of TRPC1-containing channels. Recent studies have revealed novel regulators of TRPC1-containing SOCs and have demonstrated a common molecular basis for the regulation of CRAC (calcium-release-activated calcium) and SOC channels. In the present paper, we will revisit the role of TRPC1 in SOCE and discuss how studies with TRPC1 provide an experimental basis for validating the mechanism of SOCE.
Insights
Transient Receptor Potential Canonical 1 (TRPC1) is a key component of store-operated calcium channels (SOC). Understanding TRPC1
Area of Science:
- Molecular Biology
- Cell Physiology
- Biochemistry
Background:
- Transient Receptor Potential Canonical (TRPC) proteins, particularly TRPC1, are implicated as components of store-operated calcium channels (SOC).
- TRPC1's role in store-operated calcium entry (SOCE) is established, but its regulatory mechanisms and physiological functions require further elucidation.
- TRPC1 forms signaling complexes with calcium-handling proteins within specific plasma membrane microdomains.
Purpose of the Study:
- To review the role of TRPC1 in store-operated calcium entry (SOCE).
- To discuss how TRPC1 studies validate the mechanism of SOCE.
- To explore novel regulators and the molecular basis for TRPC1-containing SOC regulation.
Main Methods:
- Review of existing literature on TRPC1 and SOCE.
- Analysis of studies on TRPC1 interactions and protein assembly.
- Discussion of novel regulatory mechanisms for TRPC1-containing channels.
Main Results:
- TRPC1 is the leading candidate for SOC channel components.
- Interactions between TRPC1 monomers and other proteins are critical for channel function and surface expression.
- Novel regulators of TRPC1-containing SOCs have been identified, revealing common regulatory principles with CRAC channels.
Conclusions:
- TRPC1 plays a significant role in SOCE.
- Understanding TRPC1 interactions and regulation provides insights into SOCE mechanisms.
- TRPC1 serves as an experimental basis for validating SOCE mechanisms.
More Related Videos
Related Concept Videos
Feedback Regulation of Calcium Concentration
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
GPCRs Regulate Adenylyl Cylase Activity
Two...
G-Protein Gated Ion Channels
Sensory organs,...
Calmodulin-dependent Signaling
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
Non-gated Ion Channels
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
Non-gated Ion Channels
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.


