Essential roles of KIF4 and its binding partner PRC1 in organized central spindle midzone formation.
A number of proteins accumulate in the anaphase spindle midzone, but the interaction and precise role of these proteins in midzone organization remain obscure. Here, we found that the microtubule-bundling protein PRC1 bound separately to the three motor proteins, KIF4, MKLP1 and CENP-E, but not to the chromosomal passenger proteins. In KIF4-deficient cells, the central spindle was disorganized, and all midzone-associated proteins including PRC1 failed to concentrate at the midline, instead being dispersed along the loosened microtubule bundles of the central spindle. This suggests that KIF4 is essential for the organization of central spindles and for midzone formation. In PRC1-deficient cells, no midzone was formed, KIF4 and CENP-E did not localize to the disconnected half-spindle, and MKLP1 and chromosomal passenger proteins localized to discrete subdomains near microtubule plus ends in the half-spindle. Thus, PRC1 is required for interaction of the two half-spindles and for localization of KIF4 and CENP-E. These results suggest that KIF4 and its binding partner PRC1 play essential roles in the organization of central spindles and midzone formation.
Cell Fate Signaling Research Unit, RIKEN (The Institute of Physical and Chemical Research), Wako, Saitama, Japan.
Yasuhiro
Y
Kurasawa
William C
WC
Earnshaw
Yuko
Y
Mochizuki
Naoshi
N
Dohmae
Kazuo
K
Todokoro
D000705:Anaphase; D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002457:Cell Extracts; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D002877:Chromosomes, Human; D017353:Gene Deletion; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D016547:Kinesins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D009363:Neoplasm Proteins; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism*; D000077022:Survivin
C107489:BIRC5 protein, human; D018797:Cell Cycle Proteins; D002457:Cell Extracts; D002868:Chromosomal Proteins, Non-Histone; D051034:Inhibitor of Apoptosis Proteins; C092935:KIF23 protein, human; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; C116662:PRC1 protein, human; D000077022:Survivin; C068688:centromere protein E; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; C484228:KIF4A protein, human; D016547:Kinesins