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 patients display abnormal chemotaxis in response to the T-cell chemoattractant stromal cell-derived factor (SDF)-1. The Wiskott- Aldrich syndrome protein (WASP), together with the Rho family GTPase Cdc42, control stimulus-induced actin cytoskeleton rearrangements that are involved in cell motility. Because WASP is an effector of Cdc42, we further studied how Cdc42 and WASP are involved in SDF-1-induced chemotaxis of T lymphocytes. We provide here direct evidence that SDF-1 activates Cdc42. We then specifically investigated the role of the interaction between Cdc42 and WASP in SDF-1-responsive cells. This was achieved by abrogating this interaction with a recombinant polypeptide (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 specifically to Cdc42-GTP and to inhibit the chemotactic response of a T-cell line to SDF-1. Altogether, these data demonstrate that Cdc42-WASP interaction is critical for SDF-1-induced chemotaxis of T cells.
Haddad
E
E
INSERM U362, Institut Gustave Roussy, Villejuif Cedex, France.
Zugaza
J L
JL
Louache
F
F
Debili
N
N
Crouin
C
C
Schwarz
K
K
Fischer
A
A
Vainchenker
W
W
Bertoglio
J
J
D000199:Actins / Q000037:antagonists & inhibitors / Q000378:metabolism; D001665:Binding Sites; D002460:Cell Line; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004347:Drug Interactions; D006801:Humans; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011506:Proteins / Q000378:metabolism* / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology; D014923:Wiskott-Aldrich Syndrome / Q000097:blood / Q000209:etiology / Q000378:metabolism; D051316:Wiskott-Aldrich Syndrome Protein; D020764:cdc42 GTP-Binding Protein / Q000187:drug effects / Q000378:metabolism / Q000494:pharmacology*; D054462:p21-Activated Kinases
D000199:Actins; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D011506:Proteins; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein; C515907:PAK2 protein, human; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D020764:cdc42 GTP-Binding Protein