Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / metabolism
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Adaptor Proteins, Signal Transducing*
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Animals
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Antigen-Presenting Cells / immunology
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Antigen-Presenting Cells / metabolism
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CD2 Antigens / metabolism*
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Carrier Proteins / immunology*
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Carrier Proteins / metabolism*
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Cytoskeletal Proteins / immunology*
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Cytoskeletal Proteins / metabolism*
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Cytoskeleton / immunology
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Cytoskeleton / metabolism
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Humans
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Jurkat Cells
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Lymphocyte Activation
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Membrane Microdomains / immunology
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Membrane Microdomains / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Proteins / immunology*
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Proteins / metabolism*
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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Wiskott-Aldrich Syndrome / immunology*
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Wiskott-Aldrich Syndrome / metabolism*
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Wiskott-Aldrich Syndrome Protein
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src Homology Domains
Substances
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Actins
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Adaptor Proteins, Signal Transducing
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CD2 Antigens
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CD2-associated protein
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Carrier Proteins
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Cytoskeletal Proteins
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PSTPIP1 protein, human
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Proteins
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Pstpip1 protein, mouse
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WAS protein, human
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Was protein, mouse
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Wiskott-Aldrich Syndrome Protein