Document Detail


Megakaryocyte lineage-specific class VI β-tubulin suppresses microtubule dynamics, fragments microtubules, and blocks cell division.
MedLine Citation:
PMID:  21309084     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Class VI β-tubulin (β6) is the most divergent tubulin produced in mammals and is found only in platelets and mature megakaryocytes. To determine how this unique tubulin isotype affects microtubule assembly and organization, we expressed the cDNA in tissue culture cells under the control of a tetracycline regulated promoter. The β6 coassembled with other endogenous β-tubulin isotypes into a normal microtubule array; but once the cells entered mitosis it caused extensive fragmentation of the microtubules, disrupted the formation of the spindle apparatus, and allowed entry into G1 phase without cytokinesis to produce large multinucleated cells. The microtubule fragments persisted into subsequent cell cycles and accumulated around the membrane in a marginal band-like appearance. The persistence of the fragments could be traced to a pronounced suppression of microtubule dynamic instability. Impairment of centrosomal nucleation also contributed to the loss of a normal microtubule cytoskeleton. Incorporation of β6 allowed microtubules to resist the effects of colcemid and maytansine, but not vinblastine or paclitaxel; however, cellular resistance to colcemid or maytansine did not occur because expression of β6 prevented cell division. The results indicate that many of the morphological features of megakaryocyte differentiation can be recapitulated in non-hematopoietic cells by β6 expression and they provide a mechanistic basis for understanding these changes.
Authors:
Hailing Yang; Anutosh Ganguly; Shanghua Yin; Fernando Cabral
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Cytoskeleton (Hoboken, N.J.)     Volume:  68     ISSN:  1949-3592     ISO Abbreviation:  Cytoskeleton (Hoboken)     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-03-10     Completed Date:  2011-06-27     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  101523844     Medline TA:  Cytoskeleton (Hoboken)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  175-87     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Wiley-Liss, Inc.
Affiliation:
Department of Integrative Biology and Pharmacology, University of Texas Medical School, Houston, Texas 77030, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetylation
Animals
CHO Cells
Cell Lineage*
Cricetinae
Cricetulus
Demecolcine / pharmacology
Humans
Maytansine / pharmacology
Megakaryocytes / drug effects*,  metabolism*
Microtubules / drug effects,  metabolism*
Mitosis / drug effects*
Mitotic Spindle Apparatus / drug effects,  metabolism
Paclitaxel / pharmacology
Tubulin / metabolism*
Tubulin Modulators / pharmacology*
Vinblastine / pharmacology
Grant Support
ID/Acronym/Agency:
CA85935/CA/NCI NIH HHS; R01 CA085935-10/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Tubulin; 0/Tubulin Modulators; 33069-62-4/Paclitaxel; 35846-53-8/Maytansine; 477-30-5/Demecolcine; 865-21-4/Vinblastine
Comments/Corrections

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