|
|
|
|
|
||
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
First published online 8 July 2008
doi: 10.1242/jcs.033001
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Research Article |
5β1 – link to focal adhesion redistribution and contractile shape
1 Division of Toxicology, Leiden Amsterdam Center for Drug Research, Einsteinweg 55, Leiden University, Leiden 2333 CC, The Netherlands
2 Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066 CX, The Netherlands
3 Department of Molecular Medicine, Max Planck Institute of Biochemistry, Am Klopferspitz 18, Martinsried, 82152, Germany
* Author for correspondence (e-mail: e.danen{at}lacdr.leidenuniv.nl)
Accepted 16 May 2008
Focal adhesions are randomly distributed across the ventral surface or along the edge of epithelial cells. In fibroblasts they orient centripetally and concentrate at a few peripheral sites connecting long F-actin stress fibers, causing a typical elongated, contractile morphology. Extensive remodeling of adhesions in fibroblasts also takes part in fibronectin fibrillogenesis, a process that depends on Rho-mediated contractility and results in the formation of a fibronectin matrix. Our current study shows that all these fibroblast characteristics are controlled by the ability of integrin 
5β1 to bind soluble fibronectin molecules in their compact inactive conformation. The hypervariable region of the ligand-binding I-like domain of integrin 5β1 supports binding of soluble fibronectin. This supports the distribution of centripetally orientated focal adhesions in distinct peripheral sites, Rho activation and fibronectin fibrillogenesis through a mechanism that does not depend on Syndecan-4. Integrin vβ3, even when locked in high affinity conformations for the RGD recognition motif shows no appreciable binding of soluble fibronectin and, consequently, fails to support the typical fibroblast focal adhesion distribution, Rho activity and fibronectin fibrillogenesis in the absence of integrin 5β1. The ability of 5β1 integrin to interact with soluble fibronectin may thus drive the cell-matrix adhesion and cytoskeletal organization required for a contractile, fibroblast-like morphology, perhaps explaining why 5β1 integrin, similarly to fibronectin, is essential for development.
Key words: Adhesion, Cytoskeleton, Extracellular matrix, Rho, Matrix assembly
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  P. Roca-Cusachs, N. C. Gauthier, A. del Rio, and M. P. Sheetz Clustering of {alpha}5{beta}1 integrins determines adhesion strength whereas {alpha}v{beta}3 and talin enable mechanotransduction PNAS, September 22, 2009; 106(38): 16245 - 16250. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Huveneers and E. H. J. Danen Adhesion signaling - crosstalk between integrins, Src and Rho J. Cell Sci., April 15, 2009; 122(8): 1059 - 1069. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Martinez-Lemus, M. A. Hill, and G. A. Meininger The Plastic Nature of the Vascular Wall: A Continuum of Remodeling Events Contributing to Control of Arteriolar Diameter and Structure Physiology, February 1, 2009; 24(1): 45 - 57. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Puklin-Faucher and M. P. Sheetz The mechanical integrin cycle J. Cell Sci., January 15, 2009; 122(2): 179 - 186. [Abstract] [Full Text] [PDF]
|
|
