Abstract
T cell polarization toward and within the cellular interface with an APC is critical for effective T cell activation. The Rho family GTPase Cdc42 is a central regulator of cellular polarization. Using live-cell imaging, we characterized the spatiotemporal patterns of Cdc42 activity and their physiological regulation. Using three independent means of experimental manipulation of Cdc42 activity, we established that Cdc42 is a critical regulator of T cell actin dynamics, TCR clustering, and cell cycle entry. Using quantification of three-dimensional data, we could relate distinct spatiotemporal patterns of Cdc42 activity to specific elements of T cell activation. This result suggests that Cdc42 activity in specific locations at specific times is most critical for its function in T cell activation.
Publication types
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Research Support, N.I.H., Extramural
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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 / physiology
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Animals
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Antigen Presentation / immunology
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Antigen-Presenting Cells / cytology
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Antigen-Presenting Cells / immunology
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Antigen-Presenting Cells / metabolism
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CD28 Antigens / physiology
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Cell Communication / immunology
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Cell Cycle / immunology
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Cell Line, Tumor
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Humans
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Lymphocyte Activation / immunology*
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Mice
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Mice, Transgenic
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Proto-Oncogene Proteins c-cbl / physiology
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Receptor Aggregation / immunology
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Receptors, Antigen, T-Cell / metabolism
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Receptors, Antigen, T-Cell / physiology
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Signal Transduction / immunology
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T-Lymphocytes / cytology*
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
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cdc42 GTP-Binding Protein / antagonists & inhibitors
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cdc42 GTP-Binding Protein / metabolism
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cdc42 GTP-Binding Protein / physiology*
Substances
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Actins
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Adaptor Proteins, Signal Transducing
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CD28 Antigens
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Cblb protein, mouse
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Receptors, Antigen, T-Cell
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Proto-Oncogene Proteins c-cbl
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cdc42 GTP-Binding Protein