Regulation of multiple cell cycle events by Cdc14 homologues in vertebrates.
Whereas early cytokinesis events have been relatively well studied, little is known about its final stage, abscission. The Cdc14 phosphatase is involved in the regulation of multiple cell cycle events, and in all systems studied Cdc14 misexpression leads to cytokinesis defects. In this work, we have cloned two CDC14 cDNA from Xenopus, including a previously unreported CDC14B homologue. We use Xenopus and human cell lines and demonstrate that localization of Cdc14 proteins is independent of both cell-type and species specificity. Ectopically expressed XCdc14A is centrosomal in interphase and localizes to the midbody in cytokinesis. By using XCdc14A misregulation, we confirm its control over different cell cycle events and unravel new functions during abscission. XCdc14A regulates the G1/S and G2/M transitions. We show that Cdc25 is an in vitro substrate for XCdc14A and might be its target at the G2/M transition. Upregulated wild-type or phosphatase-dead XCdc14A arrest cells in a late stage of cytokinesis, connected by thin cytoplasmic bridges. It does not interfere with central spindle formation, nor with the relocalization of passenger protein and centralspindlin complexes to the midbody. We demonstrate that XCdc14A upregulation prevents targeting of exocyst and SNARE complexes to the midbody, both essential for abscission to occur.
Krasinska
Liliana
L
Centre de Recherches de Biochimie Macromoleculaire, Université Montpellier II, CNRS UMR5237 1919, Route de Mende, 34293 Montpellier Cedex 5, France.
de Bettignies
Geoffroy
G
Fisher
Daniel
D
Abrieu
Ariane
A
Fesquet
Didier
D
Morin
Nathalie
N
D000199:Actins / Q000502:physiology; D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D002502:Centrioles / Q000378:metabolism* / Q000502:physiology; D003001:Cloning, Molecular; D015971:Gene Expression Regulation, Enzymologic; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000502:physiology; D050600:SNARE Proteins / Q000378:metabolism; D014981:Xenopus / Q000235:genetics* / Q000502:physiology; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D020687:cdc25 Phosphatases / Q000378:metabolism
D000199:Actins; C496855:CDC14A protein, Xenopus; D018797:Cell Cycle Proteins; D050600:SNARE Proteins; D029867:Xenopus Proteins; D049452:Green Fluorescent Proteins; D020687:cdc25 Phosphatases