title: Casein kinase I delta controls centrosome positioning during T cell activation.
abstract: Although termed central body, the centrosome is located off-center in many polarized cells. T cell receptor (TCR) engagement by antigens induces a polarity switch in T cells. This leads to the recruitment of the centrosome to the immunological synapse (IS), a specialized cell-cell junction. Despite much recent progress, how TCR signaling triggers centrosome repositioning remains poorly understood. In this paper, we uncover a critical requirement for the centrosomal casein kinase I delta (CKIδ) in centrosome translocation to the IS. CKIδ binds and phosphorylates the microtubule plus-end-binding protein EB1. Moreover, a putative EB1-binding motif at the C terminus of CKIδ is required for centrosome translocation to the IS. We find that depletion of CKIδ in T lymphocytes and inhibition of CKI in epithelial cells reduce microtubule growth. Therefore, we propose that CKIδ-EB1 complexes contribute to the increase in microtubule growth speeds observed in polarized T cells, a mechanism that might serve to generate long-stable microtubules necessary for centrosome translocation.
authors: Li Ka Shing Centre, Cancer Research UK Cambridge Research Institute, Cambridge CB2 0RE, England, UK.
authors: Deborah
authors: D
authors: Zyss
authors: Hani
authors: H
authors: Ebrahimi
authors: Fanni
authors: F
authors: Gergely
mesh_terms: D020816:Amino Acid Motifs; D001549:Benzamides / Q000494:pharmacology; D001692:Biological Transport; D048148:Casein Kinase Idelta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D016764:Cell Polarity; D018385:Centrosome / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008869:Microtubule-Associated Proteins; D008870:Microtubules / Q000378:metabolism; D010766:Phosphorylation; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure
chemical_list: C493177:4-(4-(2,3-dihydrobenzo(1,4)dioxin-6-yl)-5-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D007093:Imidazoles; C500985:MAPRE1 protein, human; D008869:Microtubule-Associated Proteins; D048148:Casein Kinase Idelta