title: PKCθ regulates T cell motility via ezrin-radixin-moesin localization to the uropod.
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.
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, New Mexico, United States of America ; Department of Pathology, University of New Mexico School of Medicine, Albuquerque, New Mexico, United States of America.
authors.forename: Judy L
authors.initials: JL
authors.lastname: Cannon
authors.forename: Francois
authors.initials: F
authors.lastname: Asperti-Boursin
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Letendre
authors.forename: Ivy K
authors.initials: IK
authors.lastname: Brown
authors.forename: Katy E
authors.initials: KE
authors.lastname: Korzekwa
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Blaine
authors.forename: Sreenivasa R
authors.initials: SR
authors.lastname: Oruganti
authors.forename: Anne I
authors.initials: AI
authors.lastname: Sperling
authors.forename: Melanie E
authors.initials: ME
authors.lastname: Moses
mesh_terms: D002465:Cell Movement / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics*; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D051917:Leukosialin / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D022101:Microtubule-Organizing Center / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics* / Q000378:metabolism; D000074121:Protein Kinase C-theta; D054400:Receptors, CCR7 / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D000099149:Ezrin
chemical_list: D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D051917:Leukosialin; D008565:Membrane Proteins; D008840:Microfilament Proteins; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta; D054400:Receptors, CCR7; D014157:Transcription Factors; D000099149:Ezrin; C515370:CCR7 protein, human; C086680:ETV5 protein, human; C465014:SPN protein, human; C071058:moesin; C071776:radixin; C076233:PRKCQ protein, human