INF2 promotes the formation of detyrosinated microtubules necessary for centrosome reorientation in T cells

Laura Andrés-Delgado; Olga M Antón; Francesca Bartolini; Ana Ruiz-Sáenz; Isabel Correas; Gregg G Gundersen; Miguel A Alonso

doi:10.1083/jcb.201202137

INF2 promotes the formation of detyrosinated microtubules necessary for centrosome reorientation in T cells

J Cell Biol. 2012 Sep 17;198(6):1025-37. doi: 10.1083/jcb.201202137.

Authors

Laura Andrés-Delgado¹, Olga M Antón, Francesca Bartolini, Ana Ruiz-Sáenz, Isabel Correas, Gregg G Gundersen, Miguel A Alonso

Affiliation

¹ Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas/Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Actins / genetics
Actins / metabolism
Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / metabolism
Cell Line, Tumor
Centrosome / metabolism*
Cytoskeletal Proteins / genetics
Cytoskeletal Proteins / metabolism
Formins
GTP-Binding Protein Regulators / genetics
GTP-Binding Protein Regulators / metabolism
Humans
Jurkat Cells
Microfilament Proteins / genetics
Microfilament Proteins / metabolism*
Microtubules / genetics
Microtubules / metabolism*
Phosphorylation
Protein Processing, Post-Translational / genetics
Protein Structure, Tertiary
Protein Subunits / genetics
Protein Subunits / metabolism
Protein Transport / genetics
Receptors, Antigen, T-Cell / genetics
Receptors, Antigen, T-Cell / metabolism
T-Lymphocytes / metabolism*
Tubulin / genetics
Tubulin / metabolism
Tyrosine / genetics
Tyrosine / metabolism*
rac1 GTP-Binding Protein / genetics
rac1 GTP-Binding Protein / metabolism

Substances

Actins
Adaptor Proteins, Signal Transducing
CDC42EP2 protein, human
Cytoskeletal Proteins
DIAPH1 protein, human
FMNL1 protein, human
Formins
GTP-Binding Protein Regulators
INF2 protein, human
Microfilament Proteins
Protein Subunits
RAC1 protein, human
Receptors, Antigen, T-Cell
Tubulin
Tyrosine
rac1 GTP-Binding Protein