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Successful completion of cytokinesis requires the spatio-temporal regulation of protein phosphorylation and the coordinated activity of protein kinases and phosphatases. Many mitotic protein kinases are well characterized while mitotic phosphatases are largely unknown. Here, we show that the Ca2+- and calmodulin-dependent phosphatase, calcineurin (CaN), is required for cytokinesis in mammalian cells, functioning specifically at the abscission stage. CaN inhibitors induce multinucleation in HeLa cells and prolong the time cells spend connected via an extended intracellular bridge. Upon Ca2+ influx during cytokinesis, CaN is activated, targeting a set of proteins for dephosphorylation, including dynamin II (dynII). At the intracellular bridge, phospho-dynII and CaN are co-localized to dual flanking midbody rings (FMRs) that reside on either side of the central midbody ring. CaN activity and disassembly of the FMRs coincide with abscission. Thus, CaN activity at the midbody plays a key role in regulating the completion of cytokinesis in mammalian cells.
Author(s): Chircop M, Malladi CS, Lian AT, Page SL, Zavortink M, Gordon CP, McCluskey A, Robinson PJ
Publication type: Article
Publication status: Published
Journal: Cellular and Molecular Life Sciences
Year: 2010
Volume: 67
Issue: 21
Pages: 3725-3737
Print publication date: 22/05/2010
ISSN (print): 1420-682X
ISSN (electronic): 1420-9071
Publisher: Birkhaeuser Verlag AG
URL: http://dx.doi.org/10.1007/s00018-010-0401-z
DOI: 10.1007/s00018-010-0401-z
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