ASAP, a human microtubule-associated protein required for bipolar spindle assembly and cytokinesis

doi:10.1073/pnas.0500964102

ASAP, a human microtubule-associated protein required for bipolar spindle assembly and cytokinesis

^*Institut de Génétique Humaine, Centre National de la Recherche Scientifique, Unité Propre de Recherche 1142, Rue de la Cardonille, 34396 Montpellier Cédex 5, France; ^†Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6061 Génétique et Développement, Groupe Cycle Cellulaire, Equipe Labellisée LNCC, Université de Rennes I, Institut Fédératif de Recherche 140, 2 Avenue du Pr Léon Bernard, 35043 Rennes, France; and ^‡Centre de Recherche de Biochimie Macromoléculaire, Centre National de la Recherche Scientifique Formation de Recherche en Évolution 2593, 1919 Route de Mende, 34293 Montpellier Cédex 5, France

Edited by J. Richard McIntosh, University of Colorado, Boulder, CO, and approved June 13, 2005 (received for review February 4, 2005)

Abstract

We have identified a unique human microtubule-associated protein (MAP) named ASAP for ASter-Associated Protein. ASAP localizes to microtubules in interphase, associates with the mitotic spindle during mitosis, localizes to the central body during cytokinesis and directly binds to purified microtubules by its COOH-terminal domain. Overexpression of ASAP induces profound bundling of cytoplasmic microtubules in interphase cells and aberrant monopolar spindles in mitosis. Depletion of ASAP by RNA interference results in severe mitotic defects: it provokes aberrant mitotic spindle, delays mitotic progression, and leads to defective cytokinesis or cell death. These results suggest a crucial role for ASAP in the organization of the bipolar mitotic spindle, mitosis progression, and cytokinesis and define ASAP as a key factor for proper spindle assembly.

mitosis

Footnotes

↵ § To whom correspondence should be addressed. E-mail: rouquier{at}igh.cnrs.fr.
Author contributions: A.A. and S.R. designed research; J.-M.S., M.V., J.E., A.A., and S.R. performed research; F.P. contributed new reagents/analytic tools; J.-M.S., M.V., C.P., D.G., A.A., and S.R. analyzed data; S.R. wrote the paper; and C.P. reviewed the manuscript.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: MT, microtubule; MAP, MT-associated protein; YFP, yellow fluorescent protein; EYFP, enhanced YFP; PFA, paraformaldehyde; siRNA, small interfering RNA.
Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AY690636).