Abstract
Docking of the centrosome at the plasma membrane directs lytic granules to the immunological synapse. To identify signals controlling centrosome docking at the synapse, we have studied cytotoxic T lymphocytes (CTLs) in which expression of the T cell receptor-activated tyrosine kinase Lck is ablated. In the absence of Lck, the centrosome is able to translocate around the nucleus toward the immunological synapse but is unable to dock at the plasma membrane. Lytic granules fail to polarize and release their contents, and target cells are not killed. In CTLs deficient in both Lck and the related tyrosine kinase Fyn, centrosome translocation is impaired, and the centrosome remains on the distal side of the nucleus relative to the synapse. These results show that repositioning of the centrosome in CTLs involves at least two distinct steps, with Lck signaling required for the centrosome to dock at the plasma membrane.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Membrane / metabolism*
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Cell Membrane / ultrastructure
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Cell Nucleus / metabolism
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Cell Nucleus / ultrastructure
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Centrosome / metabolism*
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Centrosome / ultrastructure
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Cytoplasmic Granules / metabolism
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Immunological Synapses / metabolism*
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / genetics
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / physiology*
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Mice
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Mice, Transgenic
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Proto-Oncogene Proteins c-fyn / genetics
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Proto-Oncogene Proteins c-fyn / metabolism
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Proto-Oncogene Proteins c-fyn / physiology
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Receptors, Antigen, T-Cell / metabolism
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Receptors, Antigen, T-Cell / physiology
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Signal Transduction
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T-Lymphocytes, Cytotoxic / enzymology*
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T-Lymphocytes, Cytotoxic / immunology
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T-Lymphocytes, Cytotoxic / ultrastructure
Substances
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Receptors, Antigen, T-Cell
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Fyn protein, mouse
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
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Proto-Oncogene Proteins c-fyn