Wiskott-Aldrich syndrome protein regulates lipid raft dynamics during immunological synapse formation.
Immunological synapse assembly relies on the clustering of lipid rafts and is required for optimal T cell activation. We demonstrate that the Wiskott-Aldrich syndrome protein (WASP) is recruited to lipid rafts immediately after TCR and CD28 triggering and is required for the movements of lipid rafts. T cells from Wiskott-Aldrich syndrome (WAS) patients, lacking WASP, proliferate poorly after TCR/CD28 activation and have impaired capacities to cluster the lipid raft marker GM1 and to upregulate GM1 cell surface expression. T cell proliferation and lipid raft clustering are restored by retroviral transfer of the WASP gene. These results demonstrate that WASP plays a central role in the movements of lipid rafts and identify a potential mechanism underlying the T cell defect affecting WAS patients.
San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Via Olgettina 58, 20132 Milan, Italy.
Loïc
L
Dupré
Alessandro
A
Aiuti
Sara
S
Trifari
Silvana
S
Martino
Paola
P
Saracco
Claudio
C
Bordignon
Maria-Grazia
MG
Roncarolo
D018106:CD28 Antigens / Q000276:immunology; D002118:Calcium; D002455:Cell Division; D002478:Cells, Cultured; D005677:G(M1) Ganglioside / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D021962:Membrane Microdomains / Q000276:immunology*; D011506:Proteins / Q000235:genetics / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics / Q000276:immunology*; D051316:Wiskott-Aldrich Syndrome Protein
D018106:CD28 Antigens; D011506:Proteins; D011948:Receptors, Antigen, T-Cell; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein; D005677:G(M1) Ganglioside; D002118:Calcium