title: Filamins in mechanosensing and signaling.
abstract: Filamins are essential, evolutionarily conserved, modular, multidomain, actin-binding proteins that organize the actin cytoskeleton and maintain extracellular matrix connections by anchoring actin filaments to transmembrane receptors. By cross-linking and anchoring actin filaments, filamins stabilize the plasma membrane, provide cellular cortical rigidity, and contribute to the mechanical stability of the plasma membrane and the cell cortex. In addition to binding actin, filamins interact with more than 90 other binding partners including intracellular signaling molecules, receptors, ion channels, transcription factors, and cytoskeletal and adhesion proteins. Thus, filamins scaffold a wide range of signaling pathways and are implicated in the regulation of a diverse array of cellular functions including motility, maintenance of cell shape, and differentiation. Here, we review emerging structural and functional evidence that filamins are mechanosensors and/or mechanotransducers playing essential roles in helping cells detect and respond to physical forces in their local environment.
authors.affiliation: Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Ziba
authors.initials: Z
authors.lastname: Razinia
authors.forename: Toni
authors.initials: T
authors.lastname: Mäkelä
authors.forename: Jari
authors.initials: J
authors.lastname: Ylänne
authors.forename: David A
authors.initials: DA
authors.lastname: Calderwood
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D048430:Cell Shape; D003285:Contractile Proteins / Q000737:chemistry* / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D064448:Filamins; D006801:Humans; D040542:Mechanotransduction, Cellular; D008840:Microfilament Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015398:Signal Transduction
chemical_list: D003285:Contractile Proteins; D064448:Filamins; D008840:Microfilament Proteins