Amyloid precursor-like protein 2 promotes cell migration toward fibronectin and collagen IV

Previous studies have established that in response to wounding, the express ion of amyloid precursor-like protein 2 (APLP2) in the basal cells of migra ting corneal epithelium is greatly up-regulated. To further our understandi ng of the functional significance of APLP2 in wound healing, we have measur ed the migratory response of transfected Chinese hamster ovary (CHO) cells expressing APLP2 isoforms to a variety of extracellular matrix components i ncluding laminin, collagen types I, IV, and VII, fibronectin, and heparan s ulfate proteoglycans (HSPGs). CHO cells overexpressing either of two APLP2 variants, differing in chondroitin sulfate (CS) attachment, exhibit a marke d increase in chemotaxis toward type IV collagen and fibronectin but not to laminin, collagen types I and VII, and HSPGs. Cells overexpressing APLP2-7 51 (CS-modified) exhibited a greater migratory response to fibronectin and type TV collagen than their non-CS-attached counterparts (APLP2-763), sugge sting that CS modification enhanced APLP2 effects on cell migration. Moreov er, in the presence of chlondroitin sulfate, transfectants overexpressing A PLP2-751 failed to exhibit this enhanced migration toward fibronectin, The APLP2-ECM interactions were also explored by solid phase adhesion assays. W hile overexpression of APLP2 isoforms moderately enhanced CHO adhesion to l aminin, collagen types I and VII, and HSPGs lines, especially those overexp ressing APLP2-751, exhibited greatly increased adhesion to type TV collagen and fibronectin. These observations suggest that APLP2 contributes to re-e pithelialization during wound healing by supporting epithelial cell adhesio n to fibronectin and collagen IV, thus influencing their capacity to migrat e over the wound bed. Furthermore, APLP2 interactions with fibronectin and collagen IV appear to be potentiated by the addition of a CS chain to the c ore proteins.