Editors' ChoiceCell Migration

β Integrins Dictate Mode of Movement

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Science's STKE  17 May 2005:
Vol. 2005, Issue 284, pp. tw190
DOI: 10.1126/stke.2842005tw190

Integrins are dimeric molecules consisting of one α subunit and one β subunit. The composition of integrins dictates ligand binding and cellular response (migration, attachment, and cell survival) to their interaction with the substrate or extracellular matrix. Danen et al. used cells engineered to express either β1 or β3 and showed that it is the presence of the β1 or β3 subunit that dictates whether cells move randomly or in a directed fashion. Epithelial GE11 cells engineered to express αvβ3 (GEβ3) or α5β1 (GEβ1) cells were tested in a wounding assay, or motility was monitored in sparsely seeded cultures on fibronectin. Although both cells exhibited motile behavior that was greater than the β1-deficient parent GE11 line, the GEβ3 cells moved as a sheet in a directed fashion, and the GEβ1 cells moved randomly in all directions. GEβ3 cells, but not GEβ1 cells, exhibited remodeling of the actin cytoskeleton and the formation of lamellipodia either during cell migration or in response to various treatments that trigger cell ruffling and actin cytoskeleton reorganization (epidermal growth factor, hepatocyte growth factor, or phorbol ester). In GEβ1 cells, cofilin (an actin regulator required for directed movement) was inhibited (phosphorylated), and expression of a phosphomimetic mutant cofilin inhibited lamellipodia formation in the GEβ3 cells. Use of mutants of the guanosine triphosphatases RhoA and Rac1 indicated that RhoA activity was responsible for the increased phosphorylation of cofilin in the GEβ1 cells and the highly dynamic nature of cell adhesion sites in these cells. Furthermore, although expression of activated Rac1 allowed GEβ1 cells to appear more GEβ3-like in morphology, it did not decrease cofilin phosphorylation and did not allow the cells to undergo directed movement. Thus, it appears that the efficiency of coupling of β integrins to RhoA and the degree of cofilin activation appear to generate different types of cell movement.

E. H. J. Danen, J. van Rheenen, W. Franken, S. Huveneers, P. Sonneveld, K. Jalink, A. Sonnenberg, Integrins control motile strategy through a Rho-cofilin pathway. J. Cell Biol. 169, 515-526 (2005). [Abstract] [Full Text]

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