title: Calcineurin activity is required for the completion of cytokinesis.
abstract: 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 Ca(2+)- 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 Ca(2+) 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.
authors.affiliation: Children's Medical Research Institute, The University of Sydney, 214 Hawkesbury Road, Westmead, NSW, 2145, Australia. mchircop@cmri.com.au
authors.forename: Megan
authors.initials: M
authors.lastname: Chircop
authors.forename: Chandra S
authors.initials: CS
authors.lastname: Malladi
authors.forename: Audrey T
authors.initials: AT
authors.lastname: Lian
authors.forename: Scott L
authors.initials: SL
authors.lastname: Page
authors.forename: Michael
authors.initials: M
authors.lastname: Zavortink
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Gordon
authors.forename: Adam
authors.initials: A
authors.lastname: McCluskey
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Robinson
mesh_terms: D019703:Calcineurin / Q000032:analysis / Q000378:metabolism*; D065095:Calcineurin Inhibitors; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D048749:Cytokinesis; D034285:Dynamin II / Q000032:analysis / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans
chemical_list: D065095:Calcineurin Inhibitors; D019703:Calcineurin; D034285:Dynamin II; D002118:Calcium