Document Detail


beta1 integrin cytoplasmic domain residues selectively modulate fibronectin matrix assembly and cell spreading through talin and Akt-1.
MedLine Citation:
PMID:  19144637     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The integrin beta(1) cytoplasmic domain (tail) serves as a scaffold for numerous intracellular proteins. The mechanisms by which the tail coordinates these proteins to facilitate extracellular matrix assembly and cell spreading are not clear. This study demonstrates that the beta(1) cytoplasmic domain can regulate cell spreading on fibronectin and fibronectin matrix assembly through Akt- and talin-dependent mechanisms, respectively. To identify these mechanisms, we characterized GD25 cells expressing the beta(1) integrin cytoplasmic domain mutants W775A and R760A. Although cell spreading appears normal in R760A mutant-integrin cells compared with wild type, it is inhibited in W775A mutant cells. In contrast, both mutant cell lines show defective fibronectin matrix assembly. Inhibition of cell spreading, but not matrix assembly, in the W775A mutant cells is due to a specific defect in Akt-1 activation. In addition, we find that both W775A and R760A mutant integrins have reduced surface expression of the 9EG7 epitope that correlates with reduced recruitment of talin to beta(1) integrin cytoplasmic complexes. Down-regulation of talin with small interfering RNA or expression of green fluorescent protein-talin head domain inhibits matrix assembly in beta(1) wild-type cells, mimicking the defect seen with the W775A and R760A mutant cells. These results demonstrate distinct mechanisms by which integrins regulate cell spreading and matrix assembly through the beta(1) integrin cytoplasmic tail.
Authors:
J Angelo Green; Allison L Berrier; Roumen Pankov; Kenneth M Yamada
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural     Date:  2009-01-14
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  284     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-03-16     Completed Date:  2009-05-14     Revised Date:  2011-07-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  8148-59     Citation Subset:  IM    
Affiliation:
Laboratory of Cell and Developmental Biology, NIDCR, National Institutes of Health, Bethesda, Maryland 20892, USA. angelo.green@nih.gov
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Substitution
Animals
Antigens, CD29 / genetics,  metabolism*
Cell Line
Enzyme Activation
Extracellular Matrix / genetics,  metabolism*
Fibronectins / genetics,  metabolism*
Mice
Mutation, Missense
Protein Structure, Tertiary / physiology
Proto-Oncogene Proteins c-akt / genetics,  metabolism*
RNA, Small Interfering / genetics
Talin / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Antigens, CD29; 0/Fibronectins; 0/RNA, Small Interfering; 0/Talin; EC 2.7.11.1/Akt1 protein, mouse; EC 2.7.11.1/Proto-Oncogene Proteins c-akt
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