INDIVIDUAL ISOFORMS OF THE AMYLOID-BETA PRECURSOR PROTEIN DEMONSTRATEDIFFERENTIAL ADHESIVE POTENTIALS TO CONSTITUENTS OF THE EXTRACELLULAR-MATRIX

The amyloid beta precursor protein (A beta PP) can exist as a membrane -hound glycoprotein which modulates neural cell adhesion, The adhesion of clones of the AtT20 mouse pituitary cell line, transfected with CD NA coding for the 695 (A beta PP695) and. 751 (A beta PP751) amino aci d forms of the protein, to individual components of the extracellular mats lx was determined using a centrifugal shear assay. On laminin, po ly-L-lysine, fibronectin, and uncoated glass substrata, the cells tran sfected with A beta PP695 (6A1 cells) demonstrated a 50% increase in a dhesivity over nontransfected cells, while those transfected with A be ta PP751 (7A1 cells) showed a significant decrease in adhesion. There was, however a significant increase in the adhesive strength of the 7A 1 cells to collagen type IV with no change in the adhesivity of the 6A 1 cells when compared with control. These changes in adhesivity could be attributed to changes in the levels of the membrane-bound protein a nd were not due to the interaction of soluble A beta PP with elements of the extracellular matrix. These studies provide evidence for differ ential adhesivities of the constituent A beta PP isoforms and the poss ible role of the Kunitz protease inhibitor (KPI) domain in influencing the adhesive properties of the protein backbone. (C) 1997 Wiley-Liss, Inc.