The interaction between Cdc42 and WASP is required for SDF-1-induced T-lymphocyte chemotaxis

In studies aimed at further characterizing the cellular immunodeficiency of the Wiskott-Aldrich syndrome (WAS), we found that T lymphocytes from WAS p atients display abnormal chemotaxis in response to the T-cell chemoattracta nt stromal cell-derived factor (SDF)-1, The Wiskott-Aldrich syndrome protei n (WASP), together with the Rho family GTPase Cdc42, control stimulus-induc ed actin cytoskeleton rearrangements that are involved in cell motility. Be cause WASP is an effector of Cdc42, we further studied how Cdc42 and WASP a re involved in SDF-1-induced chemotaxis of T lymphocytes, We provide here d irect evidence that SDF-1 activates Cdc42. We then specifically investigate d the role of the interaction between Cdc42: and WASP in SDF-1-responsive c ells, This was achieved by abrogating this Interaction with a recombinant p olypeptide (TAT-CRIB), comprising the Cdc42/Rac interactive binding (CRIB) domain of WASP and a human immunodeficiency virus-TAT peptide that renders the fusion protein cell-permeant, This TAT-CRIB protein was shown to bind s pecifically to Cdc42-GTP and to inhibit the chemotactic response of a T-cel l line to SDF-1. Altogether, these data demonstrate that Cdc42-WASP interac tion is critical for SDF-l-induced chemotaxis of T cells. (C) 2001 by The A merican Society of Hematology.