Ca²⁺/calmodulin kinase II-dependent regulation of β_IV-spectrin modulates cardiac fibroblast gene expression, proliferation, and contractility.

ABSTRACT: Fibrosis is a pronounced feature of heart disease and the result of dysregulated activation of resident cardiac fibroblasts (CFs). Recent work identified stress-induced degradation of the cytoskeletal protein β_IV-spectrin as an important step in CF activation and cardiac fibrosis. Furthermore, loss of β_IV-spectrin was found to depend on Ca²⁺/calmodulin-dependent kinase II (CaMKII). Therefore, we sought to determine the mechanism for CaMKII-dependent regulation of β_IV-spectrin and CF activity. Computational screening and MS revealed a critical serine residue (S2250 in mouse and S2254 in human) in β_IV-spectrin phosphorylated by CaMKII. Disruption of β_IV-spectrin/CaMKII interaction or alanine substitution of β_IV-spec

SUBMITTER: Nassal DM 

PROVIDER: S-EPMC8294584 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature