title: Spatial-temporal reorganization of activated integrins.
abstract: Integrin receptors play important roles in cell adhesion and tumor metastasis. The coupling of mechanical sensing and biochemical ligation is known to collectively regulate the activation of integrin receptors. Recently, oligomerization of activated integrins has been considered as the primordial signature of cytoskeletal remodeling and the initiation of various downstream signals, such as focal and fibrillar adhesions. However, spatio-temporal reorganization of activated integrins and associated proteins remains poorly understood. Here, we summarized the recent discovery of sequential biophysical events of integrin activation during early adhesion formation. Using the cyclic Arg-Gly-Asp (RGD) peptide as a mobile ligand on supported lipid membranes, a series of previously unreported events were observed following integrin αvβ3 clustering and cell spreading, including a long-range lateral translocation of the integrin clusters. With initial clustering, localized actin polymerization occurred in a Src family kinase dependent manner. Clustering of liganded integrins recruits various adaptor proteins and serves as a reaction core for mechanobiological activities. In addition, there are future possibilities to investigate the role of other synergetic interactions with the activated integrin receptors.
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore.
authors.forename: Cheng-han
authors.initials: CH
authors.lastname: Yu
authors.forename: Weiwei
authors.initials: W
authors.lastname: Luo
authors.forename: Michael P
authors.initials: MP
authors.lastname: Sheetz
mesh_terms: D000199:Actins / Q000378:metabolism; D001696:Biomechanical Phenomena; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D006801:Humans; D016023:Integrins / Q000378:metabolism* / Q000502:physiology; D008567:Membranes, Artificial; D008954:Models, Biological; D009842:Oligopeptides / Q000737:chemistry; D055503:Protein Multimerization; D021381:Protein Transport; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism / Q000502:physiology
chemical_list: D000199:Actins; D016023:Integrins; D008567:Membranes, Artificial; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D019061:src-Family Kinases