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Mol Cell Biol, July 1998, p. 3936-3946, Vol. 18, No. 7
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Rac Regulates Integrin-Mediated Spreading and Increased Adhesion of T Lymphocytes

Crislyn D'Souza-Schorey,1 dagger Benjamin Boettner,2 and Linda Van Aelst2 *

Department of Cell Biology, Washington University School of Medicine, St. Louis, Missouri 63110,1 and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 117242

Received 18 February 1998/Returned for modification 8 April 1998/Accepted 20 April 1998

Leukocyte adhesion to the extracellular matrix (ECM) is tightly controlled and is vital for the immune response. Circulating lymphocytes leave the bloodstream and adhere to ECM components at sites of inflammation and lymphoid tissues. Mechanisms for regulating T-lymphocyte-ECM adhesion include (i) an alteration in the affinity of cell surface integrin receptors for their extracellular ligands and (ii) an alteration of events following postreceptor occupancy (e.g., cell spreading). Whereas H-Ras and R-Ras were previously shown to affect T-cell adhesion by altering the affinity state of the integrin receptors, no signaling molecule has been identified for the second mechanism. In this study, we demonstrated that expression of an activated mutant of Rac triggered dramatic spreading of T cells and their increased adhesion on immobilized fibronectin in an integrin-dependent manner. This effect was not mimicked by expression of activated mutant forms of Rho, Cdc42, H-Ras, or ARF6, indicating the unique role of Rac in this event. The Rac-induced spreading was accompanied by specific cytoskeletal rearrangements. Also, a clustering of integrins at sites of cell adhesion and at the peripheral edges of spread cells was observed. We demonstrate that expression of RacV12 did not alter the level of expression of cell surface integrins or the affinity state of the integrin receptors. Moreover, our results indicate that Rac plays a role in the regulation of T-cell adhesion by a mechanism involving cell spreading, rather than by altering the level of expression or the affinity of the integrin receptors. Furthermore, we show that the Rac-mediated signaling pathway leading to spreading of T lymphocytes did not require activation of c-Jun kinase, serum response factor, or pp70S6 kinase but appeared to involve a phospholipid kinase.

* Corresponding author. Mailing address: Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724. Phone: (516) 367-6829. Fax: (516) 367-8815. E-mail: vanaelst{at}cshl.org.

dagger Present address: Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556.

Mol Cell Biol, July 1998, p. 3936-3946, Vol. 18, No. 7
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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