title: INF2 promotes the formation of detyrosinated microtubules necessary for centrosome reorientation in T cells.
abstract: T cell antigen receptor-proximal signaling components, Rho-family GTPases, and formin proteins DIA1 and FMNL1 have been implicated in centrosome reorientation to the immunological synapse of T lymphocytes. However, the role of these molecules in the reorientation process is not yet defined. Here we find that a subset of microtubules became rapidly stabilized and that their α-tubulin subunit posttranslationally detyrosinated after engagement of the T cell receptor. Formation of stabilized, detyrosinated microtubules required the formin INF2, which was also found to be essential for centrosome reorientation, but it occurred independently of T cell receptor-induced massive tyrosine phosphorylation. The FH2 domain, which was mapped as the INF2 region involved in centrosome repositioning, was able to mediate the formation of stable, detyrosinated microtubules and to restore centrosome translocation in DIA1-, FMNL1-, Rac1-, and Cdc42-deficient cells. Further experiments indicated that microtubule stabilization was required for centrosome polarization. Our work identifies INF2 and stable, detyrosinated microtubules as central players in centrosome reorientation in T cells.
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas/Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Andrés-Delgado
authors.forename: Olga M
authors.initials: OM
authors.lastname: Antón
authors.forename: Francesca
authors.initials: F
authors.lastname: Bartolini
authors.forename: Ana
authors.initials: A
authors.lastname: Ruiz-Sáenz
authors.forename: Isabel
authors.initials: I
authors.lastname: Correas
authors.forename: Gregg G
authors.initials: GG
authors.lastname: Gundersen
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Alonso
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D018385:Centrosome / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D000080865:Formins; D020555:GTP-Binding Protein Regulators / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000235:genetics; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D014404:Tubulin / Q000235:genetics / Q000378:metabolism; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C422984:CDC42EP2 protein, human; D003598:Cytoskeletal Proteins; C108962:DIAPH1 protein, human; C476204:FMNL1 protein, human; D000080865:Formins; D020555:GTP-Binding Protein Regulators; C546959:INF2 protein, human; D008840:Microfilament Proteins; D021122:Protein Subunits; C107953:RAC1 protein, human; D011948:Receptors, Antigen, T-Cell; D014404:Tubulin; D014443:Tyrosine; D020830:rac1 GTP-Binding Protein