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Calmodulin is responsible for Ca2+-dependent regulation of TRPA1 Channels
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Hasan, Raquibul, Leeson-Payne, Alasdair T. S., Jaggar, Jonathan H. and Zhang, Xuming (2017) Calmodulin is responsible for Ca2+-dependent regulation of TRPA1 Channels. Scientific Reports, 7 (1). 45098 . doi:10.1038/srep45098
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Official URL: http://dx.doi.org/10.1038/srep45098
Abstract
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.
| Item Type: | Journal Article | ||||||||||||||||||
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| Subjects: | Q Science > QP Physiology | ||||||||||||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||||||||||||
| Library of Congress Subject Headings (LCSH): | Calmodulin , TRP channels | ||||||||||||||||||
| Journal or Publication Title: | Scientific Reports | ||||||||||||||||||
| Publisher: | Nature Publishing Group | ||||||||||||||||||
| ISSN: | 2045-2322 | ||||||||||||||||||
| Official Date: | 23 March 2017 | ||||||||||||||||||
| Dates: |
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| Volume: | 7 | ||||||||||||||||||
| Number: | 1 | ||||||||||||||||||
| Article Number: | 45098 | ||||||||||||||||||
| DOI: | 10.1038/srep45098 | ||||||||||||||||||
| Status: | Peer Reviewed | ||||||||||||||||||
| Publication Status: | Published | ||||||||||||||||||
| Access rights to Published version: | Open Access | ||||||||||||||||||
| RIOXX Funder/Project Grant: |
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