ADAM17 Mediates Proteolytic Maturation of Voltage-Gated Calcium Channel Auxiliary α₂δ Subunits, and Enables Calcium Current Enhancement.

ABSTRACT: The auxiliary α₂δ subunits of voltage-gated calcium (Ca_V) channels are key to augmenting expression and function of Ca_V1 and Ca_V2 channels, and are also important drug targets in several therapeutic areas, including neuropathic pain. The α₂δ proteins are translated as preproteins encoding both α₂ and δ, and post-translationally proteolyzed into α₂ and δ subunits, which remain associated as a complex. In this study, we have identified ADAM17 as a key protease involved in proteolytic processing of pro-α₂δ-1 and α₂δ-3 subunits. We provide three lines of evidence: First, proteolytic cleavage is inhibited by chemical inhibitors of particular metalloproteases, including ADAM17. Second, proteolytic

SUBMITTER: Kadurin I 

PROVIDER: S-EPMC9016415 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature