The long-term goal of this research project is to understand the mechanism of cell adhesion, and involves a multidisciplinary approach using biochemical, immunological, and microscopic methods. During the past year we have characterized the FN-2 BHK cell adhesion variant and found that it is deficient in the cell-substratum contact process. That is, cell adhesion receptors are present on the surface of these cells, but the receptors cannot reorganize so as to engage in cooperative interactions. A high molecular weight glycoprotein found on parental cells is absent from the FN-2 variant and will be characterized further in the future. We also have prepared 5 monoclonal antibodies to BHK cells and are in the process of studying the effects of these antibodies on cell adhesion. Analysis of cell cytoskeletal responses to different sized fibronectin-coated beads revealed reorganization of actin and alpha actinin in response to the binding of large (5 micron beads) but not small (1 micron beads). This reorganization appeared to reflect differences in cell deformation in response to the beads. The large beads induced the formation of large cell ruffles while the small beads interacted with cell microvilli. Studies are now underway to determine whether different subsets of cell membrane coponents interact with the large and small beads. (A)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA014609-13
Application #
3163973
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1979-06-01
Project End
1987-11-30
Budget Start
1985-12-01
Budget End
1986-11-30
Support Year
13
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Type
Overall Medical
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390
Altankov, G; Grinnell, F (1993) Depletion of intracellular potassium disrupts coated pits and reversibly inhibits cell polarization during fibroblast spreading. J Cell Biol 120:1449-59
Grinnell, F; Ho, C H; Wysocki, A (1992) Degradation of fibronectin and vitronectin in chronic wound fluid: analysis by cell blotting, immunoblotting, and cell adhesion assays. J Invest Dermatol 98:410-6
Grinnell, F (1992) Wound repair, keratinocyte activation and integrin modulation. J Cell Sci 101 ( Pt 1):1-5
Mochitate, K; Pawelek, P; Grinnell, F (1991) Stress relaxation of contracted collagen gels: disruption of actin filament bundles, release of cell surface fibronectin, and down-regulation of DNA and protein synthesis. Exp Cell Res 193:198-207
Guo, M; Kim, L T; Akiyama, S K et al. (1991) Altered processing of integrin receptors during keratinocyte activation. Exp Cell Res 195:315-22
Grinnell, F; Backman, R (1991) Role of integrin receptors in manganese-dependent BHK cell spreading on albumin-coated substrata. Exp Cell Res 195:218-23
Guo, M; Toda, K; Grinnell, F (1990) Activation of human keratinocyte migration on type I collagen and fibronectin. J Cell Sci 96 ( Pt 2):197-205
Grinnell, F (1990) The activated keratinocyte: up regulation of cell adhesion and migration during wound healing. J Trauma 30:S144-9
Tuan, T L; Grinnell, F (1989) Fibronectin and fibrinolysis are not required for fibrin gel contraction by human skin fibroblasts. J Cell Physiol 140:577-83
Grinnell, F; Ho, C H; Tuan, T L (1988) Cell adhesion and phagocytosis promoted by monoclonal antibodies not directed against fibronectin receptors. J Cell Sci 90 ( Pt 2):201-14

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