INTEGRIN ALPHA-8-BETA-1 PROMOTES ATTACHMENT, CELL SPREADING, AND NEURITE OUTGROWTH ON FIBRONECTIN

The integrin alpha 8 subunit, isolated by low stringency hybridization , is a novel integrin subunit that associates with beta 1. To identify ligands, we have prepared a function-blocking antiserum to the extrac ellular domain of alpha 8, and we have established by transfection K56 2 cell lines that stably express alpha 8 beta 1 heterodimers on the ce ll surface. We demonstrate here by cell adhesion and neurite outgrowth assays that alpha 8 beta 1 is a fibronectin receptor. Studies on fibr onectin fragments using RGD peptides as inhibitors show that alpha 8 b eta 1 binds to the RGD site of fibronectin. In contrast to the endogen ous alpha 5 beta 1 fibronectin receptor in K562 cells, alpha 8 beta 1 not only promotes cell attachment but also extensive cell spreading, s uggesting functional differences between the two receptors. In chick e mbryo fibroblasts, alpha 8 beta 1 is localized to focal adhesions. We conclude that alpha 8 beta 1 is a receptor for fibronectin and can pro mote attachment, cell spreading, and neurite outgrowth on fibronectin.