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Published 24 December 2001. doi:10.1083/jcb.200107107
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© The Rockefeller University Press, 0021-9525/2001/12/1319 $5.00
The Journal of Cell Biology, Volume 155, Number 7, December 24, 2001 1319-1332


Article

Marching at the front and dragging behind

: differential {alpha}Vß3-integrin turnover regulates focal adhesion behavior



Christoph Ballestrem, Boris Hinz, Beat A. Imhof and Bernhard Wehrle-Haller

Department of Pathology, Centre Médical Universitaire, Geneva, Switzerland

Address correspondence to Bernhard Wehrle-Haller, Dept. of Pathology, Centre Médical Universitaire, 1, Rue Michel-Servet, 1211 Geneva 4, Switzerland. Tel.: 0041-22-702-57-35. Fax: 0041-22-702-57-46. E-mail: Bernhard.Wehrle-Haller{at}medecine.unige.ch

Integrins are cell–substrate adhesion molecules that provide the essential link between the actin cytoskeleton and the extracellular matrix during cell migration. We have analyzed {alpha}Vß3-integrin dynamics in migrating cells using a green fluorescent protein–tagged ß3-integrin chain. At the cell front, adhesion sites containing {alpha}Vß3-integrin remain stationary, whereas at the rear of the cell they slide inward. The integrin fluorescence intensity within these different focal adhesions, and hence the relative integrin density, is directly related to their mobility. Integrin density is as much as threefold higher in sliding compared with stationary focal adhesions. High intracellular tension under the control of RhoA induced the formation of high-density contacts. Low-density adhesion sites were induced by Rac1 and low intracellular tension. Photobleaching experiments demonstrated a slow turnover of ß3-integrins in low-density contacts, which may account for their stationary nature. In contrast, the fast ß3-integrin turnover observed in high-density contacts suggests that their apparent sliding may be caused by a polarized renewal of focal contacts. Therefore, differential acto-myosin–dependent integrin turnover and focal adhesion densities may explain the mechanical and behavioral differences between cell adhesion sites formed at the front, and those that move in the retracting rear of migrating cells.

Key Words: cell migration; cell adhesion; green fluorescent protein; Rho GTPases; integrin density


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