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Published online 27 June 2005. doi:10.1083/jcb.200412032
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 170, Number 1, 141-151
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Article

 A talin-dependent LFA-1 focal zone is formed by rapidly migrating T lymphocytes

Andrew Smith1, Yolanda R. Carrasco2, Paula Stanley1, Nelly Kieffer3, Facundo D. Batista2, and Nancy Hogg1

1 Leukocyte Adhesion Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, England, UK
2 Lymphocyte Interaction Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, England, UK
3 Laboratoire de Biologie et Physiologie Intégrée, Université du Luxembourg, L-1511 Luxembourg, Luxembourg

Correspondence to N. Hogg: nancy.hogg{at}cancer.org.uk

Cells such as fibroblasts and endothelial cells migrate through the coordinated responses of discrete integrin-containing focal adhesions and complexes. In contrast, little is known about the organization of integrins on the highly motile T lymphocyte. We have investigated the distribution, activity, and cytoskeletal linkage of the integrin lymphocyte function associated antigen-1 (LFA-1) on human T lymphocytes migrating on endothelial cells and on ligand intercellular adhesion molecule-1 (ICAM-1). The pattern of total LFA-1 varies from low expression in the lamellipodia to high expression in the uropod. However, high affinity, clustered LFA-1 is restricted to a mid-cell zone that remains stable over time and over a range of ICAM-1 densities. Talin is essential for the stability and formation of the LFA-1 zone. Disruption of the talin–integrin link leads to loss of zone integrity and a substantial decrease in speed of migration on ICAM-1. This adhesive structure, which differs from the previously described integrin-containing attachments displayed by many other cell types, we have termed the "focal zone."

Abbreviations used in this paper: DIC, differential interference contrast; FA, focal adhesion; FC, focal complex; HUVEC, human umbilical vein endothelial cell; ICAM-1, intercellular adhesion molecule-1; IRM, interference reflection microscopy; LFA-1, lymphocyte function associated antigen-1; PIPKI{gamma}, phosphatidylinositol phosphate kinase type I{gamma}; PLL, poly-L-lysine; ROCK, Rho kinase.


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