title: Assembly and disassembly of cell matrix adhesions.
abstract: The formation of tissues and organs requires cells to adhere to each other and/or to migrate and polarize in contact with components of the extracellular matrix. The connection between the cytoskeleton and the extracellular environment is provided by heterodimeric transmembrane receptors of the integrin family. In response to extracellular ligand binding, integrins undergo a conformational switch that permits the recruitment of cytoplasmic adapter proteins, eventually linking the integrin receptors to the actin cytoskeleton, progressively forming highly complex cell-matrix adhesions. A major challenge in the field consists in identifying the regulatory mechanisms, which drive the assembly of cell-matrix adhesions as they are based on posttranslational modifications as well as allosteric conformational changes caused by protein-protein as well as protein-lipid interactions. In response to mechanical tension, generated either by intra-cellular acto-myosin contraction, shear stress or mechanical strain on the extracellular scaffold, the composition and signaling of cell-matrix adhesion changes, leading either to increased anchorage or controlled disassembly of cell matrix adhesions, both processes critically involved in cell migration. The aim of this review is to provide insight into the mechanisms leading to the progressive assembly of focal adhesions, how they are modulated in response to mechanical challenges and which mechanisms are used for their disassembly.
authors: University of Geneva, Department of Cell Physiology and Metabolism, Centre Médical Universitaire, 1. Rue Michel-Servet, 1211 Geneva 4, Switzerland. Bernhard.Wehrle-Haller@unige.ch
authors: Bernhard
authors: B
authors: Wehrle-Haller
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002465:Cell Movement; D021982:Cell-Matrix Junctions / Q000737:chemistry / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D016608:Talin / Q000737:chemistry / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D000099200:Scaffold Protein ILK
chemical_list: D002352:Carrier Proteins; D016023:Integrins; D017346:Protein Serine-Threonine Kinases; D016608:Talin; D020830:rac1 GTP-Binding Protein; D000099200:Scaffold Protein ILK