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Updated: Jun 30, 2026
Cell-based Calcium Assay for Medium to High Throughput Screening of TRP Channel Functions using FlexStation 3
Published on: August 17, 2011
Multiple roles of calmodulin and other Ca(2+)-binding proteins in the functional regulation of TRP channels
1Department of Neuroscience and the Center for Molecular Neurobiology, The Ohio State University, 168 Rightmire Hall, 1060 Carmack Road, Columbus, OH 43210, USA. zhu.55@osu.edu
Abstract:
Transient receptor potential channels (TRP) have emerged as cellular sensors of various internal and external cues. Generally, the activation of TRP canonical (TRPC) channels is triggered by the stimulation of phospholipase C; however, multiple factors are involved in the regulation of these channels. Among them, Ca(2+)-mediated feedback channel modulations are often mediated by calmodulin (CaM) and other Ca(2+)-binding proteins. In vitro binding studies have revealed multiple CaM-binding sites on TRPC proteins. Among them, a common CaM/inositol 1,4,5-trisphosphate receptor-binding site is found at the carboxyl terminus of every TRPC isoform. Additional non-conserved CaM-binding sites are present at the amino and carboxyl termini of several TRPC proteins. Likewise, multiple CaM-binding sites were found in other TRP proteins. These, together with the presence in close vicinity of the interaction sites for the related neuronal Ca(2+)-binding proteins, such as CaBP1, suggest a multitude of diverse intracellular Ca(2+)-dependent regulations of TRP channels. Functional studies have begun to reveal the unique roles of CaM and CaBP1 binding to several TRP channels. This review will focus on the CaM- and CaBP1-mediated regulations of TRPC channels. Related studies on TRPM and TRPV channels will also be highlighted.
Insights
Transient receptor potential (TRP) channels are cellular sensors regulated by calcium. Calmodulin (CaM) and CaBP1 binding sites on TRP channels, particularly TRPC, reveal diverse calcium-dependent regulatory mechanisms.
Area of Science:
- Cellular Biology
- Molecular Physiology
- Ion Channel Function
Background:
- Transient receptor potential (TRP) channels act as cellular sensors for internal and external stimuli.
- TRP canonical (TRPC) channel activation typically involves phospholipase C, but is subject to complex regulation.
- Calcium (Ca2+)-dependent feedback mechanisms, often involving calmodulin (CaM), are critical for TRP channel modulation.
Purpose of the Study:
- To review the Ca2+-dependent regulatory mechanisms of TRPC channels.
- To highlight the roles of calmodulin (CaM) and Ca2+-binding protein 1 (CaBP1) in TRPC channel function.
- To discuss CaM and CaBP1 interactions with other TRP channel subtypes (TRPM, TRPV).
Main Methods:
- In vitro binding assays to identify CaM-binding sites on TRPC proteins.
- Analysis of conserved and non-conserved CaM-binding domains across TRPC isoforms.
- Review of functional studies investigating the impact of CaM and CaBP1 binding on TRP channel activity.
Main Results:
- Multiple CaM-binding sites identified on TRPC proteins, including a conserved site at the carboxyl terminus.
- Additional non-conserved CaM-binding sites exist on amino and carboxyl termini of various TRPC proteins.
- Proximity of CaM and CaBP1 interaction sites suggests intricate Ca2+-dependent regulatory networks for TRP channels.
Conclusions:
- Calmodulin (CaM) and CaBP1 play significant roles in the diverse intracellular Ca2+-dependent regulation of TRPC channels.
- Understanding these interactions is crucial for elucidating TRP channel function in cellular signaling.
- Further research into CaM/CaBP1-TRP channel interactions will illuminate their physiological and pathological relevance.
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