Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

Analysis of Fibronectin Receptor Function with Monoclonal Antibodies: Roles in Cell Adhesion, Migration, Matrix Assembly, and Cytoskeletal Organization

Steven K. Akiyama, Susan S. Yamada, Wen-Tien Chen and Kenneth M. Yamada
The Journal of Cell Biology
Vol. 109, No. 2 (Aug., 1989), pp. 863-875
Stable URL: http://www.jstor.org/stable/1613628
Page Count: 13
  • More info
  • Cite this Item
Analysis of Fibronectin Receptor Function with Monoclonal Antibodies: Roles in Cell Adhesion, Migration, Matrix Assembly, and Cytoskeletal Organization
Preview not available

Abstract

We have developed two rat mAbs that recognize different subunits of the human fibroblast fibronectin receptor complex and have used them to probe the function of this cell surface heterodimer. mAb 13 recognizes the integrin class 1 beta polypeptide and mAb 16 recognizes the fibronectin receptor alpha polypeptide. We tested these mAbs for their inhibitory activities in cell adhesion, spreading, migration, and matrix assembly assays using WI38 human lung fibroblasts. mAb 13 inhibited the initial attachment as well as the spreading of WI38 cells on fibronectin and laminin substrates but not on vitronectin. Laminin-mediated adhesion was particularly sensitive to mAb 13. In contrast, mAb 16 inhibited initial cell attachment to fibronectin substrates but had no effect on attachment to either laminin or vitronectin substrates. When coated on plastic, both mAbs promoted WI38 cell spreading. However, mAb 13 (but not mAb 16) inhibited the radial outgrowth of cells from an explant on fibronectin substrates. mAb 16 also did not inhibit the motility of individual fibroblasts on fibronectin in low density culture and, in fact, substantially accelerated migration rates. In assays of the assembly of an extracellular fibronectin matrix by WI38 fibroblasts, both mAbs produced substantial inhibition in a concentration-dependent manner. The inhibition of matrix assembly resulted from impaired retention of fibronectin on the cell surface. Treatment of cells with mAb 16 also resulted in a striking redistribution of cell surface fibronectin receptors from a streak-like pattern to a relatively diffuse distribution. Concomitant morphological changes included decreases in thick microfilament bundle formation and reduced adhesive contacts of the streak-like and focal contact type. Our results indicate that the fibroblast fibronectin receptor (a) functions in initial fibroblast attachment and in certain types of adhesive contact, but not in the later steps of cell spreading; (b) is not required for fibroblast motility but instead retards migration; and (c) is critically involved in fibronectin retention and matrix assembly. These findings suggest a central role for the fibronectin receptor in regulating cell adhesion and migration.

Page Thumbnails

  • Thumbnail: Page 
863
    863
  • Thumbnail: Page 
864
    864
  • Thumbnail: Page 
865
    865
  • Thumbnail: Page 
866
    866
  • Thumbnail: Page 
867
    867
  • Thumbnail: Page 
868
    868
  • Thumbnail: Page 
869
    869
  • Thumbnail: Page 
870
    870
  • Thumbnail: Page 
871
    871
  • Thumbnail: Page 
872
    872
  • Thumbnail: Page 
873
    873
  • Thumbnail: Page 
874
    874
  • Thumbnail: Page 
875
    875