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MBC in Press, published online ahead of print March 30, 2005
Mol. Biol. Cell 10.1091/mbc.E04-09-0773

A more recent version of this article appeared on June 1, 2005
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Submitted on September 3, 2004
Revised on March 11, 2005
Accepted on March 17, 2005

Clues to CD2AP Involvement in Cytokinesis

Pascale Monzo,* Nils C. Gauthier,{dagger} Frédérique Keslair,* Agnès Loubat,{ddagger} Christine M. Field,{sect} Yannick Le Marchand-Brustel,* and Mireille Cormont*

*Institut National de la Santé et de la Recherche Médicale U568, Faculté de Médecine, 06107 Nice Cedex 02, France; {dagger}Institut National de la Santé et de la Recherche Médicale U627, Faculté de Médecine, 06107 Nice Cedex 02, France; {ddagger}Institut Fédératif de Recherche 50, Faculté de Médecine, 06107 Nice Cedex 02, France; {sect}Department of Systems Biology, Harvard Medical School, Boston, MA 02115

Monitoring Editor: Anne Ridley

Cytokinesis requires membrane trafficking coupled to actin remodeling and involves a number of trafficking molecules. CD2-associated protein (CD2AP) has been implicated in dynamic actin remodeling and membrane trafficking that occurs during endocytosis leading to the degradative pathway. In this study, we present several arguments for its implication in cytokinesis. First, endogenous CD2AP was found concentrated in the narrow region of the midzone microtubules during anaphase and in the midbody during late telophase. Moreover, we found that CD2AP is a membrane- and not a microtubule-associated protein. Second, the overexpression of the first two SH3 domains of CD2AP, which are responsible for this localization, led to a significant increase in the rate of cell multinucleation. Third, the CD2AP siRNA interfered with the cell separation, indicating that CD2AP is required for HeLa cells cytokinesis. Fourth, using the yeast two hybrid system CD2AP was found to interact with anillin, a specific cleavage furrow component, and the two proteins colocalized at the midbody. Both CD2AP and anillin were found phosphorylated early in mitosis and, also, CD2AP phosphorylation was coupled to its delocalization from membrane to cytosol. All these observations led us to propose CD2AP as a new player in cytokinesis.

Address correspondence to: Mireille Cormont (cormont{at}unice.fr)






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