Document Detail

Phenotypic consequences of beta1-tubulin expression and MAP4 decoration of microtubules in adult cardiocytes.
MedLine Citation:
PMID:  12855424     Owner:  NLM     Status:  MEDLINE    
In pressure-overload cardiac hypertrophy, microtubule network densification is one cause of contractile dysfunction. Cardiac transcriptional upregulation of beta1-tubulin rather than the constitutive beta4-tubulin and of microtubule-associated protein (MAP)4 accompanies hypertrophy, with extensive microtubule decoration by MAP4. Because MAP4 stabilizes microtubules, and because the isoform-variable carboxy terminus of beta-tubulin binds to MAP4, we wished to determine whether one or both of these proteins has etiologic significance for cardiac microtubule network densification. Recombinant adenoviruses encoding beta1-tubulin, beta4-tubulin, and MAP4 were used to infect isolated cardiocytes. Overexpressed MAP4 caused a shift of tubulin dimers to the polymerized fraction and formation of a dense, stable microtubule network. Overexpressed beta1- or beta4-tubulin had neither any independent effect on these variables nor any effect additive to that of simultaneously overexpressed MAP4. Results from transgenic mice with cardiac overexpression of beta1-tubulin or MAP4 were confirmatory, but unlike the effects of brief adenovirus-mediated MAP4 overexpression in isolated cardiocytes, MAP4 transgenic hearts showed a marked increase in total alpha- and beta-tubulin. Thus MAP4 overexpression caused increased tubulin expression, formation of stable microtubules, and altered microtubule network properties, such that MAP4 upregulation may be one cause for the dense, stable microtubule network characteristic of pressure-overloaded, hypertrophied cardiocytes.
Masaru Takahashi; Hirokazu Shiraishi; Yuji Ishibashi; Kristie L Blade; Paul J McDermott; Donald R Menick; Dhandapani Kuppuswamy; George Cooper
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.     Date:  2003-07-10
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  285     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2003 Nov 
Date Detail:
Created Date:  2003-10-16     Completed Date:  2003-11-21     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H2072-83     Citation Subset:  IM    
Gazes Cardiac Research Institute, PO Box 250773, Medical University of South Carolina, 114 Doughty Street, Charleston, SC 29403, USA.
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MeSH Terms
Adenoviridae / genetics
Age Factors
Cardiomegaly / metabolism,  physiopathology
Cells, Cultured
Gene Transfer Techniques
Mice, Transgenic
Microtubule-Associated Proteins / genetics*,  metabolism
Microtubules / physiology*
Myocytes, Cardiac / cytology,  physiology*
Myosin Heavy Chains / genetics
Promoter Regions, Genetic
Tubulin / genetics*,  metabolism
Grant Support
Reg. No./Substance:
0/MAP4; 0/Microtubule-Associated Proteins; 0/Myosin Heavy Chains; 0/Tubulin

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