Document Detail


A novel function of heparan sulfate in the regulation of cell-cell fusion.
MedLine Citation:
PMID:  19726670     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Despite the important contribution of cell-cell fusion in the development and physiology of eukaryotes, little is known about the mechanisms that regulate this process. Our study shows that glycosaminoglycans and more specifically heparan sulfate (HS) expressed on the cell surface and extracellular matrix may act as negative regulator of cell-cell fusion. Using herpes simplex virus type-1 as a tool to enhance cell-cell fusion, we demonstrate that the absence of HS expression on the cell surface results in a significant increase in cell-cell fusion. An identical phenomenon was observed when other viruses or polyethylene glycol was used as fusion enhancer. Cells deficient in HS biosynthesis showed increased activity of two Rho GTPases, RhoA and Cdc42, both of which showed a correlation between increased activity and increased cell-cell fusion. This could serve as a possible explanation as to why HS-deficient cells showed significantly enhanced cell-cell fusion and suggests that HS could regulate fusion via fine tuning of RhoA and Cdc42 activities.
Authors:
Christopher D O'Donnell; Deepak Shukla
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-09-02
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  284     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-10-19     Completed Date:  2009-11-23     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  29654-65     Citation Subset:  IM    
Affiliation:
Department of Ophthalmology and Visual Sciences and the Department of Microbiology and Immunology, College of Medicine, University of Illinois, Chicago, Illinois 60612, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
CHO Cells
Cell Fusion
Cercopithecus aethiops
Cricetinae
Cricetulus
HeLa Cells
Heparitin Sulfate / genetics,  metabolism,  pharmacology*
Herpesvirus 1, Human / metabolism
Humans
Vero Cells
cdc42 GTP-Binding Protein / genetics,  metabolism*
rhoA GTP-Binding Protein / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
R01 AI057860/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
124671-05-2/RHOA protein, human; 9050-30-0/Heparitin Sulfate; EC 3.6.5.2/cdc42 GTP-Binding Protein; EC 3.6.5.2/rhoA GTP-Binding Protein
Comments/Corrections

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