Calmodulin binding is required for calcium mediated TRPA1 desensitization.

ABSTRACT: TRPA1 is an essential calcium (Ca²⁺)-permeable channel involved in nociception and inflammation. It exhibits complex and mechanistically elusive Ca²⁺ regulation with initial potentiation then rapid desensitization. We find that the universal Ca²⁺ sensor Calmodulin (CaM) binds TRPA1 in cells at rest and suppresses channel activity. Combining biochemical, biophysical, modeling, NMR spectroscopy, and functional approaches, we identify an evolutionarily conserved, high-affinity Ca²⁺/CaM binding element in the TRPA1 distal C-terminus. Genetic or biochemical perturbation of Ca²⁺/CaM binding to this site yields hyperactive channels that exhibit drastic slowing of desensitization with minor effect on potentiation. Higher extracellular Ca²

SUBMITTER: Sanders JH 

PROVIDER: S-EPMC12485084 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature