Article
- The EMBO Journal (2006) 25, 4740 - 4751
- doi:10.1038/sj.emboj.7601324
Published online: 5 October 2006
Subject Category:
A PI3K activity-independent function of p85 regulatory subunit in control of mammalian cytokinesis
Zaira García, Virginia Silio, Miriam Marqués, Isabel Cortés, Amit Kumar, Carmen Hernandez, Ana I Checa, Antonio Serrano and Ana C Carrera
- Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain
Correspondence to:
Ana C Carrera, Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Darwin 3, Campus de Cantoblanco, Madrid 28049, Spain. Tel.: +34 91 585 4846; Fax: +34 91 372 0493; E-mail: acarrera@cnb.uam.es
Received 28 February 2006; Accepted 14 August 2006
Abstract
Cytosolic division in mitotic cells involves the function of a number of cytoskeletal proteins, whose coordination in the spatio-temporal control of cytokinesis is poorly defined. We studied the role of p85/p110 phosphoinositide kinase (PI3K) in mammalian cytokinesis. Deletion of the p85
regulatory subunit induced cell accumulation in telophase and appearance of binucleated cells, whereas inhibition of PI3K activity did not affect cytokinesis. Moreover, reconstitution of p85-deficient cells with a 
p85 mutant, which does not bind the catalytic subunit, corrected the cytokinesis defects of p85-/- cells. We analyzed the mechanism by which p85 regulates cytokinesis; p85 deletion reduced Cdc42 activation in the cleavage furrow and septin 2 accumulation at this site. As Cdc42 deletion also triggered septin 2 and cytokinesis defects, a mechanism by which p85 controls cytokinesis is by regulating the local activation of Cdc42 in the cleavage furrow and in turn septin 2 localization. We show that p85 acts as a scaffold to bind Cdc42 and septin 2 simultaneously. p85 is thus involved in the spatial control of cytosolic division through regulation of Cdc42 and septin 2, in a PI3K-activity independent manner.
Keywords:
- cell cycle,
- cytokinesis,
- p85 regulatory subunit,
- phosphatidylinositol 3-kinase
