Calmodulin binding is required for calcium mediated TRPA1 desensitization.

ABSTRACT: Calcium (Ca²⁺) ions affect nearly all aspects of biology. Excessive Ca²⁺ entry is cytotoxic and Ca²⁺-mobilizing receptors have evolved diverse mechanisms for tight regulation that often include Calmodulin (CaM). TRPA1, an essential Ca²⁺-permeable ion channel involved in pain signaling and inflammation, exhibits complex Ca²⁺ regulation with initial channel potentiation followed by rapid desensitization. The molecular mechanisms of TRPA1 Ca²⁺ regulation and whether CaM plays a role remain elusive. We find that TRPA1 binds CaM best at basal Ca²⁺ concentration, that they co-localize in resting cells, and that CaM suppresses TRPA1 activity. Combining biochemical, biophysical, modeling, NMR spectroscopy, and functional

SUBMITTER: Sanders JH 

PROVIDER: S-EPMC11661184 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature