WD40-repeat protein 62 is a JNK-phosphorylated spindle pole protein required for spindle maintenance and timely mitotic progression.
The impact of aberrant centrosomes and/or spindles on asymmetric cell division in embryonic development indicates the tight regulation of bipolar spindle formation and positioning that is required for mitotic progression and cell fate determination. WD40-repeat protein 62 (WDR62) was recently identified as a spindle pole protein linked to the neurodevelopmental defect of microcephaly but its roles in mitosis have not been defined. We report here that the in utero electroporation of neuroprogenitor cells with WDR62 siRNAs induced their cell cycle exit and reduced their proliferative capacity. In cultured cells, we demonstrated cell-cycle-dependent accumulation of WDR62 at the spindle pole during mitotic entry that persisted until metaphase-anaphase transition. Utilizing siRNA depletion, we revealed WDR62 function in stabilizing the mitotic spindle specifically during metaphase. WDR62 loss resulted in spindle orientation defects, decreased the integrity of centrosomes displaced from the spindle pole and delayed mitotic progression. Additionally, we revealed JNK phosphorylation of WDR62 is required for maintaining metaphase spindle organization during mitosis. Our study provides the first functional characterization of WDR62 and has revealed requirements for JNK/WDR62 signaling in mitotic spindle regulation that may be involved in coordinating neurogenesis.
Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Victoria 3010,  Australia.
Marie A
MA
Bogoyevitch
Yvonne Y C
YY
Yeap
Zhengdong
Z
Qu
Kevin R
KR
Ngoei
Yan Y
YY
Yip
Teresa T
TT
Zhao
Julian I
JI
Heng
Dominic C H
DC
Ng
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D018385:Centrosome / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D005260:Female; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008677:Metaphase; D051379:Mice; D008810:Mice, Inbred C57BL; D008831:Microcephaly; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D009419:Nerve Tissue Proteins; D058953:Neural Stem Cells / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation; D011418:Prophase; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics; D008941:Spindle Apparatus / Q000378:metabolism*
D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; C581545:WDR62 protein, mouse; D048031:JNK Mitogen-Activated Protein Kinases