The Wiskott-Aldrich syndrome protein acts downstream of CD2 and the CD2AP and PSTPIP1 adaptors to promote formation of the immunological synapse.
The Wiskott-Aldrich syndrome protein (WASp) couples actin cytoskeletal rearrangement to T cell activation, but the mechanisms involved are unknown. Here, we show that antigen-induced formation of T cell:APC conjugates and synapses is abrogated in WASp-deficient T cells and that CD2 engagement evokes interactions between the proline-rich region required for WASp translocation to the synapse and the PSTPIP1 adaptor SH3 domain and between the PSTPIp1 coiled-coil domain and both CD2 and another CD2-binding adaptor, CD2AP. The induced colocalization of these proteins at the synapse is disrupted by expression of coiled-coil domain-deleted PSTPIP1. These data, together with the impairment in CD2-induced actin polymerization observed in WASp-deficient cells, suggest that PSTPIP1 acts downstream of CD2/CD2AP to link CD2 engagement to the WASp-evoked actin polymerization required for synapse formation and T cell activation.
Badour
Karen
K
Department of Medical Genetics and Microbiology, University of Toronto, 600 University Avenue, Toronto, M5G 1X5 Ontario, Canada.
Zhang
Jinyi
J
Shi
Fabio
F
McGavin
Mary K H
MK
Rampersad
Vik
V
Hardy
Lynne A
LA
Field
Deborah
D
Siminovitch
Katherine A
KA
D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D018801:CD2 Antigens / Q000378:metabolism*; D002352:Carrier Proteins / Q000276:immunology* / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000276:immunology* / Q000378:metabolism*; D003599:Cytoskeleton / Q000276:immunology / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D021962:Membrane Microdomains / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011506:Proteins / Q000276:immunology* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014923:Wiskott-Aldrich Syndrome / Q000276:immunology* / Q000378:metabolism*; D051316:Wiskott-Aldrich Syndrome Protein; D018909:src Homology Domains
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D018801:CD2 Antigens; C114545:CD2-associated protein; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C486382:PSTPIP1 protein, human; D011506:Proteins; C110097:Pstpip1 protein, mouse; C495767:WAS protein, human; C495768:Was protein, mouse; D051316:Wiskott-Aldrich Syndrome Protein