Document Detail


Urokinase anchors uPAR to the actin cytoskeleton.
MedLine Citation:
PMID:  15326109     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: To investigate the expression and localization of urokinase plasminogen activator (uPA) and its receptor (uPAR) and their interaction with the actin cytoskeleton in human corneal fibroblasts. METHODS: Primary cultured human corneal fibroblasts were exposed to exogenous uPA to investigate its effect on the distribution of uPAR under resting conditions and in a scrape-wound model. Fluorescence microscopy, immunolocalization, immunoprecipitation, and the actin depolymerizing drug cytochalasin D were used to evaluate uPAR's interaction with the actin cytoskeleton. RESULTS: uPA/uPAR was immunodetected in large (200 microm2) aggregates devoid of detectable F-actin. However, when uPA was added to corneal fibroblasts before fixation, a dynamic association between uPAR and the actin cytoskeleton was revealed: the uPA/uPAR complex was immunodetected throughout the surface of the plasma membrane in the form of dispersed small aggregates (0.05 microm2). Association of uPAR with actin stress fibers was visualized when FITC-labeled uPA was added to the cells. This codistribution of uPA/uPAR and actin was not detected when the cells were pretreated with the actin-depolymerizing drug, cytochalasin D. uPAR was found also in focal adhesions, the termination points of F-actin, where it colocalized with the integrin alphavbeta3 in cells migrating into a scrape wound. Coimmunoprecipitation experiments confirmed the physical association of uPAR with alphavbeta3 in fibroblasts. CONCLUSIONS: The authors propose that uPA/uPAR ligation anchors the complex to the actin cytoskeleton and is a part of the mechanism responsible for uPA-induced cell migration in fibroblasts.
Authors:
Audrey M Bernstein; Roseanne S Greenberg; Lavinia Taliana; Sandra K Masur
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  45     ISSN:  0146-0404     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2004 Sep 
Date Detail:
Created Date:  2004-08-24     Completed Date:  2004-10-07     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2967-77     Citation Subset:  IM    
Copyright Information:
Copyright Association for Research in Vision and Ophthalmology
Affiliation:
Department of Ophthalmology, Monut Sinai School of Medicine, New York, New York 10029-6574, USA. audrey.bernstein@mssm.edu
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MeSH Terms
Descriptor/Qualifier:
Actins / metabolism*
Adult
Cell Membrane / metabolism
Cell Movement
Cells, Cultured
Cornea / metabolism*
Cytochalasin D / pharmacology
Cytoskeleton / metabolism*
Fibroblasts / drug effects,  metabolism*,  physiology
Focal Adhesions / metabolism
Humans
Immunohistochemistry / methods
Integrin alphaVbeta3 / metabolism
Middle Aged
Models, Biological
Receptors, Cell Surface / metabolism*
Receptors, Urokinase Plasminogen Activator
Staining and Labeling
Tissue Distribution
Urokinase-Type Plasminogen Activator / metabolism*,  pharmacology
Grant Support
ID/Acronym/Agency:
F32 EY07049/EY/NEI NIH HHS; R01 EY09414/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Actins; 0/Integrin alphaVbeta3; 0/PLAUR protein, human; 0/Receptors, Cell Surface; 0/Receptors, Urokinase Plasminogen Activator; 22144-77-0/Cytochalasin D; EC 3.4.21.73/Urokinase-Type Plasminogen Activator

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