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The Journal of Immunology, 2006, 177: 1708-1720.
Copyright © 2006 by The American Association of Immunologists

Specific Patterns of Cdc42 Activity Are Related to Distinct Elements of T Cell Polarization1

Irina Tskvitaria-Fuller*, Abhinav Seth{dagger}, Neeta Mistry{dagger}, Hua Gu{ddagger}, Michael K. Rosen{dagger},§ and Christoph Wülfing2,*,¶

* Center for Immunology, and {dagger} Department of Biochemistry, University of Texas (UT) Southwestern Medical Center, Dallas, TX 75390; {ddagger} Department of Microbiology and Immunology, Columbia University School of Physicians and Surgeons, New York, NY 10032; and § Howard Hughes Medical Institute, and Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX 75390

T cell polarization toward and within the cellular interface with an APC is critical for effective T cell activation. The Rho family GTPase Cdc42 is a central regulator of cellular polarization. Using live-cell imaging, we characterized the spatiotemporal patterns of Cdc42 activity and their physiological regulation. Using three independent means of experimental manipulation of Cdc42 activity, we established that Cdc42 is a critical regulator of T cell actin dynamics, TCR clustering, and cell cycle entry. Using quantification of three-dimensional data, we could relate distinct spatiotemporal patterns of Cdc42 activity to specific elements of T cell activation. This result suggests that Cdc42 activity in specific locations at specific times is most critical for its function in T cell activation.




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