Document Detail

Mechanisms of spindle-pole organization are influenced by kinetochore activity in mammalian cells.
MedLine Citation:
PMID:  17276919     Owner:  NLM     Status:  MEDLINE    
The spindle is a fusiform bipolar-microtubule array that is responsible for chromosome segregation during mitosis. Focused poles are an essential feature of spindles in vertebrate somatic cells, and pole focusing has been shown to occur through a centrosome-independent self-organization mechanism where microtubule motors cross-link and focus microtubule minus ends. Most of our understanding of this mechanism for pole focusing derives from studies performed in cell-free extracts devoid of centrosomes and kinetochores. Here, we examine how sustained force from kinetochores influences the mechanism of pole focusing in cultured cells. We show that the motor-driven self-organization activities associated with NuMA (i.e., cytoplasmic dynein) and HSET are not necessary for pole focusing if sustained force from kinetochores is inhibited in Nuf2- or Mis12-deficient cells. Instead, pole organization relies on TPX2 as it cross-links spindle microtubules to centrosome-associated mitotic asters. Thus, both motor-driven and static-cross-linking mechanisms contribute to spindle-pole organization, and kinetochore activity influences the mechanism of spindle-pole organization. The motor-driven self-organization of microtubule minus ends at spindle poles is needed to organize spindle poles in vertebrate somatic cells when kinetochores actively exert force on spindle microtubules.
Amity L Manning; Duane A Compton
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Current biology : CB     Volume:  17     ISSN:  0960-9822     ISO Abbreviation:  Curr. Biol.     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-02-05     Completed Date:  2007-06-04     Revised Date:  2008-05-14    
Medline Journal Info:
Nlm Unique ID:  9107782     Medline TA:  Curr Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  260-5     Citation Subset:  IM    
Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
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MeSH Terms
Antigens, Nuclear / metabolism
Cell Cycle Proteins / metabolism
Cell-Free System
Cells, Cultured
Green Fluorescent Proteins / metabolism
Kinetochores / metabolism*
Microtubule-Associated Proteins / metabolism
Microtubules / metabolism*
Mitotic Spindle Apparatus / metabolism*
Nuclear Matrix-Associated Proteins / metabolism
Nuclear Proteins / metabolism
RNA, Small Interfering
Grant Support
Reg. No./Substance:
0/Antigens, Nuclear; 0/Cell Cycle Proteins; 0/MIS12 protein, human; 0/Microtubule-Associated Proteins; 0/NUF2 protein, human; 0/NUMA1 protein, human; 0/Nuclear Matrix-Associated Proteins; 0/Nuclear Proteins; 0/RNA, Small Interfering; 0/TPX2 protein, human; 147336-22-9/Green Fluorescent Proteins

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