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The dynamic complexity of the TRPC1 channelosome.
Channels (Austin). 2011 Sep-Oct; 5(5):424-31.C

Abstract

A rise in cytoplasmic [Ca2+] due to store-operated Ca2+ entry (SOCE) triggers a plethora of responses, both acute and long term. This leads to the important question of how this initial signal is decoded to regulate specific cellular functions. It is now clearly established that local [Ca2+] at the site of SOCE can vary significantly from the global [Ca2+] in the cytosol. Such Ca2+ microdomains are generated by the assembly of key Ca2+ signaling proteins within the domains. For example, GPCR, IP 3 receptors, TRPC3 channels, the plasma membrane Ca2+ pump and the endoplasmic reticulum (ER) Ca2+ pump have all been found to be assembled in a complex and all of them contribute to the Ca2+ signal. Recent studies have revealed that two other critical components of SOCE, STIM1 and Orai1, are also recruited to these regions. Thus, the entire machinery for activation and regulation of SOCE is compartmentalized in specific cellular domains which facilitates the specificity and rate of protein-protein interactions that are required for activation of the channels. In the case of TRPC1-SOC channels, it appears that specific lipid domains, lipid raft domains (LRDs), in the plasma membrane, as well as cholesterol-binding scaffolding proteins such as caveolin-1 (Cav-1), are involved in assembly of the TRPC channel complexes. Thus, plasma membrane proteins and lipid domains as well as ER proteins contribute to the SOCE-Ca2+ signaling microdomain and modulation of the Ca2+ signals per se. Of further interest is that modulation of Ca2+ signals, i.e. amplitude and/or frequency, can result in regulation of specific cellular functions. The emerging data reveal a dynamic Ca2+ signaling complex composed of TRPC1/Orai1/STIM1 that is physiologically consistent with the dynamic nature of the Ca2+ signal that is generated. This review will focus on the recent studies which demonstrate critical aspects of the TRPC1 channelosome that are involved in the regulation of TRPC1 function and TRPC1-SOC-generated Ca2+ signals.

Authors+Show Affiliations

Secretory Physiology Section, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.No affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

21747233

Citation

Ong, Hwei Ling, and Indu S. Ambudkar. "The Dynamic Complexity of the TRPC1 Channelosome." Channels (Austin, Tex.), vol. 5, no. 5, 2011, pp. 424-31.
Ong HL, Ambudkar IS. The dynamic complexity of the TRPC1 channelosome. Channels (Austin). 2011;5(5):424-31.
Ong, H. L., & Ambudkar, I. S. (2011). The dynamic complexity of the TRPC1 channelosome. Channels (Austin, Tex.), 5(5), 424-31. https://doi.org/10.4161/chan.5.5.16471
Ong HL, Ambudkar IS. The Dynamic Complexity of the TRPC1 Channelosome. Channels (Austin). 2011 Sep-Oct;5(5):424-31. PubMed PMID: 21747233.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The dynamic complexity of the TRPC1 channelosome. AU - Ong,Hwei Ling, AU - Ambudkar,Indu S, Y1 - 2011/09/01/ PY - 2011/7/13/entrez PY - 2011/7/13/pubmed PY - 2012/2/15/medline SP - 424 EP - 31 JF - Channels (Austin, Tex.) JO - Channels (Austin) VL - 5 IS - 5 N2 - A rise in cytoplasmic [Ca2+] due to store-operated Ca2+ entry (SOCE) triggers a plethora of responses, both acute and long term. This leads to the important question of how this initial signal is decoded to regulate specific cellular functions. It is now clearly established that local [Ca2+] at the site of SOCE can vary significantly from the global [Ca2+] in the cytosol. Such Ca2+ microdomains are generated by the assembly of key Ca2+ signaling proteins within the domains. For example, GPCR, IP 3 receptors, TRPC3 channels, the plasma membrane Ca2+ pump and the endoplasmic reticulum (ER) Ca2+ pump have all been found to be assembled in a complex and all of them contribute to the Ca2+ signal. Recent studies have revealed that two other critical components of SOCE, STIM1 and Orai1, are also recruited to these regions. Thus, the entire machinery for activation and regulation of SOCE is compartmentalized in specific cellular domains which facilitates the specificity and rate of protein-protein interactions that are required for activation of the channels. In the case of TRPC1-SOC channels, it appears that specific lipid domains, lipid raft domains (LRDs), in the plasma membrane, as well as cholesterol-binding scaffolding proteins such as caveolin-1 (Cav-1), are involved in assembly of the TRPC channel complexes. Thus, plasma membrane proteins and lipid domains as well as ER proteins contribute to the SOCE-Ca2+ signaling microdomain and modulation of the Ca2+ signals per se. Of further interest is that modulation of Ca2+ signals, i.e. amplitude and/or frequency, can result in regulation of specific cellular functions. The emerging data reveal a dynamic Ca2+ signaling complex composed of TRPC1/Orai1/STIM1 that is physiologically consistent with the dynamic nature of the Ca2+ signal that is generated. This review will focus on the recent studies which demonstrate critical aspects of the TRPC1 channelosome that are involved in the regulation of TRPC1 function and TRPC1-SOC-generated Ca2+ signals. SN - 1933-6969 UR - https://www.unboundmedicine.com/medline/citation/21747233/The_dynamic_complexity_of_the_TRPC1_channelosome_ L2 - https://www.tandfonline.com/doi/full/10.4161/chan.5.5.16471 DB - PRIME DP - Unbound Medicine ER -