Abstract
Cell motility is a fundamental process crucial for function in many cell types, including T cells. T cell motility is critical for T cell-mediated immune responses, including initiation, activation, and effector function. While many extracellular receptors and cytoskeletal regulators have been shown to control T cell migration, relatively few signaling mediators have been identified that can modulate T cell motility. In this study, we find a previously unknown role for PKCθ in regulating T cell migration to lymph nodes. PKCθ localizes to the migrating T cell uropod and regulates localization of the MTOC, CD43 and ERM proteins to the uropod. Furthermore, PKCθ-deficient T cells are less responsive to chemokine induced migration and are defective in migration to lymph nodes. Our results reveal a novel role for PKCθ in regulating T cell migration and demonstrate that PKCθ signals downstream of CCR7 to regulate protein localization and uropod formation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Cell Movement / genetics*
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Cytoskeletal Proteins / metabolism
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DNA-Binding Proteins / metabolism
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Humans
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Immunity, Cellular / genetics*
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Isoenzymes / genetics*
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Isoenzymes / metabolism
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Leukosialin / metabolism
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Lymph Nodes / metabolism
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Lymph Nodes / pathology
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Membrane Proteins / metabolism
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Microfilament Proteins / metabolism
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Microtubule-Organizing Center / metabolism
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Protein Kinase C / genetics*
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Protein Kinase C / metabolism
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Protein Kinase C-theta
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Receptors, CCR7 / metabolism*
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism*
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Transcription Factors / metabolism
Substances
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CCR7 protein, human
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Cytoskeletal Proteins
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DNA-Binding Proteins
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ETV5 protein, human
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Isoenzymes
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Leukosialin
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Membrane Proteins
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Microfilament Proteins
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Receptors, CCR7
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SPN protein, human
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Transcription Factors
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ezrin
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moesin
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radixin
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PRKCQ protein, human
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Protein Kinase C
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Protein Kinase C-theta