Referencia

Current Biology (2012) 22:1516-23.

Autores

Sdelci S*, Schütz M*, Pinyol R, Bertran MT, Regué L, Caelles C, Vernos I, Roig J. (*These authors contributed equally to this work)

Resumen

The accumulation of g-tubulin at the centrosomes during maturation is a key mechanism that ensures the formation of two dense microtubule (MT) asters in cells entering mitosis, defining spindle pole positioning and ensuring the faithful outcome of cell division. Centrosomal g-tubulin recruitment depends on the adaptor protein NEDD1/GCP-WD and is controlled by the kinase Plk1. Surprisingly, and although Plk1 binds and phosphorylates NEDD1 at multiple sites, the mechanism by which this kinase promotes the centrosomal recruitment of g-tubulin has remained elusive. Using Xenopus egg extracts and mammalian cells, we now show that it involves Nek9, a NIMA-family kinase required for normal mitotic progression and spindle organization. Nek9 phosphorylates NEDD1 on Ser377 driving its recruitment and thereby that of g-tubulin to the centrosome in mitotic cells. This role of Nek9 requires its activation by Plk1-dependent phosphorylation but is independent from the downstream related kinases Nek6 and Nek7. Our data contribute to understand the mechanism by which Plk1 promotes the recruitment of g-tubulin to the centro- some in dividing cells and position Nek9 as a key regulator of centrosome maturation.

Descripción

Los centrosomas son los principales centros de organización de microtúbulos de las células que los poseen. Durante la entrada en mitosis estos orgánulos "maduran", acumulando diferentes proteínas que les permitirán nuclear y organizar los microtúbulos necesarios para la formación del huso mitótico. En este trabajo describimos como, controlada por Plk1 y durante la entrada en mitosis, la quinasa de la familia NIMA Nek9 regula la acumulación centrosomal de una proteína clave para este proceso, el adaptador Nedd1, y como resultado el complejo nucleador de microtúbulos γ-TuRC. Se propone así un mecanismo que contribuye a comprender a nivel molecular la regulación de la maduración y su dependencia de Plk1.

imagen enero

REFERENCIA DEL GRUPO INVESTIGADOR

Los grupos de Joan Roig (IRB Barcelona) y Isabelle Vernos (CRG) colaboran en el estudio de la función de las proteína quinasas de la familia NIMA utilizando diferentes sistemas, líneas celulares de vertebrado y extractos de huevos de Xenopus laevis. El objetivo de esta colaboración es comprender mejor como estas quinasas regulan la formación del huso mitótico y la segregación de los cromosomas durante la mitosis.

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