PKCθ regulates T cell motility via ezrin-radixin-moesin localization to the uropod

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...

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Bibliographic Details
Published in:PloS one 2013-11, Vol.8 (11), p.e78940-e78940
Main Authors: Cannon, Judy L, Asperti-Boursin, Francois, Letendre, Kenneth A, Brown, Ivy K, Korzekwa, Katy E, Blaine, Kelly M, Oruganti, Sreenivasa R, Sperling, Anne I, Moses, Melanie E
Format: Article
Language:English
Subjects:
CC chemokine receptors
CCR7 protein
CD43 antigen
Cell activation
Cell adhesion & migration
Cell migration
Cell Movement - genetics
Cytoskeletal Proteins - metabolism
Cytoskeleton
DNA-Binding Proteins - metabolism
Ezrin
Humans
Immune response (cell-mediated)
Immunity, Cellular - genetics
Isoenzymes - genetics
Isoenzymes - metabolism
Kinases
Leukosialin - metabolism
Localization
Lymph nodes
Lymph Nodes - metabolism
Lymph Nodes - pathology
Lymphocytes
Lymphocytes T
Membrane Proteins - metabolism
Microfilament Proteins - metabolism
Microtubule-Organizing Center - metabolism
Moesin
Protein kinase C
Protein Kinase C - genetics
Protein Kinase C - metabolism
Protein Kinase C-theta
Proteins
Radixin
Receptor mechanisms
Receptors
Receptors, CCR7 - metabolism
Regulators
Signaling
T cell receptors
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
Transcription Factors - metabolism
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0078940