Aurora A phosphorylation of WD40-repeat protein 62 in mitotic spindle regulation

Lim, Nicholas R., Yeap, Yvonne Y. C., Ang, Ching-Seng, Williamson, Nicholas A., Bogoyevitch, Marie A., Quinn, Leonie M. and Ng, Dominic C. H. (2016) Aurora A phosphorylation of WD40-repeat protein 62 in mitotic spindle regulation. Cell Cycle, 15 3: 413-424. doi:10.1080/15384101.2015.1127472


Author Lim, Nicholas R.
Yeap, Yvonne Y. C.
Ang, Ching-Seng
Williamson, Nicholas A.
Bogoyevitch, Marie A.
Quinn, Leonie M.
Ng, Dominic C. H.
Title Aurora A phosphorylation of WD40-repeat protein 62 in mitotic spindle regulation
Journal name Cell Cycle   Check publisher's open access policy
ISSN 1538-4101
1551-4005
Publication date 2016-02
Year available 2016
Sub-type Article (original research)
DOI 10.1080/15384101.2015.1127472
Open Access Status Not yet assessed
Volume 15
Issue 3
Start page 413
End page 424
Total pages 12
Place of publication Philadelphia, PA United States
Publisher Taylor &Francis
Collection year 2017
Language eng
Abstract Mitotic spindle organization is regulated by centrosomal kinases that potentiate recruitment of spindle-associated proteins required for normal mitotic progress including the microcephaly protein WD40-repeat protein 62 (WDR62). WDR62 functions underlie normal brain development as autosomal recessive mutations and wdr62 loss cause microcephaly. Here we investigate the signaling interactions between WDR62 and the mitotic kinase Aurora A (AURKA) that has been recently shown to cooperate to control brain size in mice. The spindle recruitment of WDR62 is closely correlated with increased levels of AURKA following mitotic entry. We showed that depletion of TPX2 attenuated WDR62 localization at spindle poles indicating that TPX2 co-activation of AURKA is required to recruit WDR62 to the spindle. We demonstrated that AURKA activity contributed to the mitotic phosphorylation of WDR62 residues Ser49 and Thr50 and phosphorylation of WDR62 N-terminal residues was required for spindle organization and metaphase chromosome alignment. Our analysis of several MCPH-associated WDR62 mutants (V65M, R438H and V1314RfsX18) that are mislocalized in mitosis revealed that their interactions and phosphorylation by AURKA was substantially reduced consistent with the notion that AURKA is a key determinant of WDR62 spindle recruitment. Thus, our study highlights the role of AURKA signaling in the spatiotemporal control of WDR62 at spindle poles where it maintains spindle organization.
Keyword Aurora A
C-jun N-terminal kinase
Mitosis
Phosphorylation
Primary microcephaly
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Biomedical Sciences Publications
 
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