Document Detail


WD40-repeat protein 62 is a JNK-phosphorylated spindle pole protein required for spindle maintenance and timely mitotic progression.
MedLine Citation:
PMID:  22899712     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Marie A Bogoyevitch; Yvonne Y C Yeap; Zhengdong Qu; Kevin R Ngoei; Yan Y Yip; Teresa T Zhao; Julian I Heng; Dominic C H Ng
Publication Detail:
Type:  Journal Article     Date:  2012-08-16
Journal Detail:
Title:  Journal of cell science     Volume:  125     ISSN:  1477-9137     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2013-01-01     Completed Date:  2013-06-10     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  5096-109     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Victoria 3010, Australia.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Cell Cycle Proteins / genetics,  metabolism*
Cell Proliferation
Centrosome / metabolism
Cerebral Cortex / metabolism,  pathology
Female
Gene Knockdown Techniques
HeLa Cells
Humans
JNK Mitogen-Activated Protein Kinases / metabolism*
Metaphase*
Mice
Mice, Inbred C57BL
Microcephaly
Microtubule-Associated Proteins / genetics,  metabolism*
Microtubules / metabolism
Mitotic Spindle Apparatus / metabolism*
Neural Stem Cells / metabolism,  physiology
Phosphorylation
Prophase
Protein Processing, Post-Translational*
Protein Transport
RNA, Small Interfering / genetics
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Microtubule-Associated Proteins; 0/RNA, Small Interfering; 0/WDR62 protein, mouse; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  AtTPR7 is a chaperone docking protein of the Sec translocon in Arabidopsis.
Next Document:  PKA isoforms coordinate mRNA fate during nutrient starvation.