Extracellular Cysteines Are Critical to Form Functional Cx46 Hemichannels.

ABSTRACT: Connexin (Cxs) hemichannels participate in several physiological and pathological processes, but the molecular mechanisms that control their gating remain elusive. We aimed at determining the role of extracellular cysteines (Cys) in the gating and function of Cx46 hemichannels. We studied Cx46 and mutated all of its extracellular Cys to alanine (Ala) (one at a time) and studied the effects of the Cys mutations on Cx46 expression, localization, and hemichannel activity. Wild-type Cx46 and Cys mutants were expressed at comparable levels, with similar cellular localization. However, functional experiments showed that hemichannels formed by the Cys mutants did not open either in response to membrane depolarization or removal of extracellular divalent cations. Molecular-dynamics simulations sho

SUBMITTER: Fernandez-Olivares A 

PROVIDER: S-EPMC9266770 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature