A PI3K activity-independent function of p85 regulatory subunit in control of mammalian cytokinesis

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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 p85α regulatory subunit induced cell accumulation in telophase and appearance of binucleated cells, whereas inhibition of PI3K activity did not affect cytokinesis. Moreover, reconstitution of p85α‐deficient cells with a Δp85α mutant, which does not bind the catalytic subunit, corrected the cytokinesis defects of p85α−/− cells. We analyzed the mechanism by which p85α regulates cytokinesis; p85α 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.