Document Detail


hTPX2 is required for normal spindle morphology and centrosome integrity during vertebrate cell division.
MedLine Citation:
PMID:  12477396     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Bipolar spindle formation is essential for the accurate segregation of genetic material during cell division. Although centrosomes influence the number of spindle poles during mitosis, motor and non-motor microtubule-associated proteins (MAPs) also play key roles in determining spindle morphology. TPX2 is a novel MAP also characterized in Xenopus cell-free extracts. To examine hTPX2 (human TPX2) function in human cells, we used siRNA to knock-down its expression and found that cells lacking hTPX2 arrest in mitosis with multipolar spindles. NuMA, gamma-tubulin, and centrin localize to each pole, and nocodazole treatment of cells lacking hTPX2 demonstrates that the localization of gamma-tubulin to multiple spindle poles requires intact microtubules. Furthermore, we show that the formation of monopolar microtubule arrays in human cell extracts does not require hTPX2, demonstrating that the mechanism by which hTPX2 promotes spindle bipolarity is independent of activities focusing microtubule minus ends at spindle poles. Finally, inhibition of the kinesin Eg5 in hTPX2-depleted cells leads to monopolar spindles, indicating that Eg5 function is necessary for multipolar spindle formation in the absence of hTPX2. Our observations reveal a structural role for hTPX2 in spindles and provide evidence for a balance between microtubule-based motor forces and structural spindle components.
Authors:
Sarah Garrett; Kristi Auer; Duane A Compton; Tarun M Kapoor
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Current biology : CB     Volume:  12     ISSN:  0960-9822     ISO Abbreviation:  Curr. Biol.     Publication Date:  2002 Dec 
Date Detail:
Created Date:  2002-12-12     Completed Date:  2003-07-29     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9107782     Medline TA:  Curr Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  2055-9     Citation Subset:  IM    
Affiliation:
Laboratory of Chemistry and Cell Biology, Rockefeller University, New York, NY 10021, USA.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/BG389502
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Cycle / genetics,  physiology*
Cell Cycle Proteins*
Cell Division / physiology*
Centrosome / ultrastructure*
Cloning, Molecular
Expressed Sequence Tags
Hela Cells
Humans
Interphase
Microtubule-Associated Proteins / genetics,  metabolism*
Mitosis
Mitotic Spindle Apparatus / ultrastructure*
Molecular Sequence Data
Neoplasm Proteins*
Nuclear Proteins*
Phosphoproteins*
Recombinant Proteins / metabolism
Vertebrates
Xenopus Proteins*
Grant Support
ID/Acronym/Agency:
GM51542/GM/NIGMS NIH HHS; GM65933/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Microtubule-Associated Proteins; 0/Neoplasm Proteins; 0/Nuclear Proteins; 0/Phosphoproteins; 0/Recombinant Proteins; 0/TPX2 protein, Xenopus; 0/TPX2 protein, human; 0/Xenopus Proteins

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


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