Calmodulin is responsible for Ca2+-dependent regulation of TRPA1 Channels

R Hasan, AT Leeson-Payne, JH Jaggar, X Zhang

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TRPA1 is a Ca2+-permeable ion channel involved in many sensory disorders such as pain, itch and neuropathy. Notably, the function of TRPA1 depends on Ca2+, with low Ca2+ potentiating and high Ca2+ inactivating TRPA1. However, it remains unknown how Ca2+ exerts such contrasting effects. Here, we show that Ca2+ regulates TRPA1 through calmodulin, which binds to TRPA1 in a Ca2+-dependent manner. Calmodulin binding enhanced TRPA1 sensitivity and Ca2+-evoked potentiation of TRPA1 at low Ca2+, but inhibited TRPA1 sensitivity and promoted TRPA1 desensitization at high Ca2+. Ca2+-dependent potentiation and inactivation of TRPA1 were selectively prevented by disrupting the interaction of the carboxy-lobe of calmodulin with a calmodulin-binding domain in the C-terminus of TRPA1. Calmodulin is thus a critical Ca2+ sensor enabling TRPA1 to respond to diverse Ca2+ signals distinctly.

Original languageEnglish
Article number45098
Number of pages13
JournalScientific Reports
Publication statusPublished - 23 Mar 2017

Bibliographical note

RH was supported by a PhD studentship from the Islamic Development Bank and the Cambridge Commonwealth Trust. ATSLP was supported by a BBSRC EastBio Ph. D studentship. This work was partly funded by an MRC new investigator research grant (to XZ) and a Royal Society project grant (to XZ).

Corrigendum: Calmodulin is responsible for Ca2+-dependent regulation of TRPA1 Channels, Raquibul Hasan, Alasdair T.S. Leeson-Payne, Jonathan H. Jaggar, Xuming Zhang, 2017, vol. 7, p. 46588. Scientific reports


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