The adhesion of cells to collagen is of fundamental significance to many of the key events in normal and pathologic biology including primary hemostasis. This process can be initiated by the adhesion and subsequent activation of platelets by exposed subendothelial collagen. The experiments outlined in this proposal are directed toward delineating at the cellular and molecular level the mechanisms by which platelets and possibly other cell types interact directly with collagen. I will characterize and unambiguously establish the role in platelet-collagen adhesion of a 160/130 kDa, Mg++-dependent collagen binding protein recently isolated from platelet membranes in my laboratory. This protein complex is the likely mediator of a Mg++-dependent mechanism of platelet-collagen adhesion recently shown by my laboratory to support a rate and extent of adhesion far greater than the more frequently studied divalent cation-independent mechanism. The relationship between the Mg++-dependent and divalent cation- independent mechanisms of adhesion will be established by the combined use of biochemical and immunochemical approaches. The association of the 160/130 kDa collagen binding protein with the platelet cytoskeleton will be established. I will also examine the participation of the 160/130 kDa complex in ligand induced clustering on the platelet surface as previously proposed in our model for the role of multiple, simultaneous, and linked interactions in platelet-collagen adhesion. Finally, I will establish the presence and function of proteins immunochemically related to the platelet surface collagen binding complex on the surfaces of other cell types. Our very recent observation that the platelet surface collagen binding complex is specifically immunoprecipitated by the monoclonal antibody 12F1 which defines the alpha subunit of the VLA-2 antigen which is present on other cells lends further credence to the hypothesis that other cell types adhere to collagen by mechanisms similar or identical to that employed by platelets.
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