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Speaker Professor Dieter Fürst, Department of Molecular Cell Biology, Institute for Cell Biology, University of Bonn, Germany.

Title The role of filamin C for muscle maintenance under mechanical stress

Host Mathias Gautel

 

Abstract Mechanical force-induced conformational changes in proteins underpin a variety of physiological functions, typified by the contractile machinery of muscle. Mutations in the actin-binding protein filamin C (FLNc) that localises to sarcomeric Z-disks, costameres and intercalated discs are linked to musculoskeletal and cardiac pathologies including myofibrillar myopathy and a variety of cardiomyopathies, and are characterised by altered biomechanical properties and sometimes protein aggregates. FLNc is a mechanosensitive protein whose interaction with additional ligands, including chaperones and components of chaperone-assisted selective autophagy (CASA), is regulated both directly by mechanical cues and mechanosensitive modulation of binding sites by exposure of phosphorylation sites. This may represent a posttranslationally regulated chaperone-client protection mechanism accelerating repair from over-extension during mechanical stress.

FLNc, a modular structural protein, thus serves as a paradigm of muscle cytoskeletal mechanosignalling; its interlinked cytoskeletal and signalling roles in mechanically regulated proteostasis now also allow a better mechanistic understanding of the pathophysiological effects of FLNc mutations in various myopathies and cardiomyopathies.