Role of Filamin C in Muscle Cells

Abstract

Filamin C (FLNC) is a member of a high-molecular weight protein family, which bind actin filaments in the cytoskeleton of various cells. In human genome FLNC is encoded by the FLNC gene located on chromosome 7 and is expressed predominantly in striated skeletal and cardiac muscle cells. Filamin C is involved in organization and stabilization of thin actin filaments three-dimensional network in sarcomeres, and is supposed to play a role of mechanosensor transferring mechanical signals to different protein targets. Under mechanical stress FLNC can undergo unfolding that increases the risk of its aggregation. FLNC molecules with an impaired native structure could be eliminated by the BAG3-mediated chaperone-assisted selective autophagy. Mutations in the FLNC gene could be accompanied by the changes in FLNC interaction with its protein partners and could lead to formation of aggregates, which overload the autophagy and proteasome protein degradation systems, thus facilitating development of various pathological processes. Molecular mechanisms of the FLNC-associated congenital disorders, called filaminopathies, remain poorly understood. This review is devoted to analysis of the structure and mechanisms of filamin C function in muscle and heart cells in normal state and in the FLNC-associated pathologies. The presented data summarize the results of research at the molecular, cellular, and tissue levels and allow us to outline promising ways for further investigation of pathogenetic mechanisms in filaminopathies.