Spatiotemporal control of spindle midzone formation by PRC1 in human cells.
We have examined the role of PRC1, a midzone-associated, microtubule bundling, Cdk substrate protein, in regulating the spatiotemporal formation of the midzone in HeLa cells. Cdk-mediated phosphorylation of PRC1 in early mitosis holds PRC1 in an inactive monomeric state. During the metaphase-to-anaphase transition, PRC1 is dephosphorylated, promoting PRC1 oligomerization. Using time-lapse video microscopy, RNA interference, 3D immunofluorescence reconstruction imaging, and rescue experiments, we demonstrate that the dephosphorylated form of PRC1 is essential for bundling antiparallel, nonkinetochore, interdigitating microtubules to establish the midzone that is necessary for cytokinesis. Our results thus indicate that PRC1 is an essential factor in controlling the spatiotemporal formation of the midzone in human cells.
Zhu
Changjun
C
The Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Lau
Eric
E
Schwarzenbacher
Robert
R
Bossy-Wetzel
Ella
E
Jiang
Wei
W
D016203:CDC2 Protein Kinase / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D019926:Cyclin B / Q000378:metabolism; D006801:Humans; D016547:Kinesins / Q000235:genetics; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D008941:Spindle Apparatus / Q000378:metabolism* / Q000648:ultrastructure
D018797:Cell Cycle Proteins; D019926:Cyclin B; C116662:PRC1 protein, human; D034741:RNA, Small Interfering; D016203:CDC2 Protein Kinase; C484228:KIF4A protein, human; D016547:Kinesins