Structure and Function of Filamin C in the Muscle Z-Disc

• Published in: International journal of molecular sciences Vol. 21; no. 8; p. 2696
• Main Authors: Mao, Zhenfeng, Nakamura, Fumihiko
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 13.04.2020; MDPI
• Subjects: Actin; Amino acid sequence; Amino acids; Animals; Binding; Binding sites; Calpain; Cardiomyopathy; Carrier Proteins; Crosslinking; Dimerization; Domains; Filaments; Filamin C; filaminopathy; Filamins - chemistry; Filamins - metabolism; FLNC; Humans; Models, Molecular; Molecular Structure; Muscle Cells - metabolism; Muscle Cells - ultrastructure; Muscle contraction; Muscles; Muscular Diseases - etiology; Muscular Diseases - metabolism; Muscular function; Musculoskeletal system; Mutation; Myogenesis; NMR; Nuclear magnetic resonance; Phosphorylation; Protein Binding; Protein Conformation; Protein kinase C; Protein Processing, Post-Translational; Proteins; Review; sarcomere; Sarcomeres; Sarcomeres - metabolism; Sarcomeres - ultrastructure; Structure-Activity Relationship; Structure-function relationships; Z-disc; filaminopathy; mutation; Z-disc; myopathy; Filamin C; FLNC; sarcomere
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21082696

Filamin C (FLNC) is one of three filamin proteins (Filamin A (FLNA), Filamin B (FLNB), and FLNC) that cross-link actin filaments and interact with numerous binding partners. FLNC consists of a N-terminal actin-binding domain followed by 24 immunoglobulin-like repeats with two intervening calpain-sensitive hinges separating R15 and R16 (hinge 1) and R23 and R24 (hinge-2). The FLNC subunit is dimerized through R24 and calpain cleaves off the dimerization domain to regulate mobility of the FLNC subunit. FLNC is localized in the Z-disc due to the unique insertion of 82 amino acid residues in repeat 20 and necessary for normal Z-disc formation that connect sarcomeres. Since phosphorylation of FLNC by PKC diminishes the calpain sensitivity, assembly, and disassembly of the Z-disc may be regulated by phosphorylation of FLNC. Mutations of FLNC result in cardiomyopathy and muscle weakness. Although this review will focus on the current understanding of FLNC structure and functions in muscle, we will also discuss other filamins because they share high sequence similarity and are better characterized. We will also discuss a possible role of FLNC as a mechanosensor during muscle contraction.