Collagen receptor control of epithelial morphogenesis and cell cycle progression

To define the unique contributions of the a subunit cytoplasmic tails of th e alpha(1)beta(1) and alpha(2)beta(1) integrin to epithelial differentiatio n and branching morphogenesis, a variant NMuMG cell line lacking alpha(1)be ta(1) and alpha(2)beta(1) integrin expression was stably transfected with t he full-length alpha(2) integrin subunit cDNA (X2C2), chimeric cDNA consist ing of the extracellular and transmembrane domains of the alpha(2) subunit and the cytoplasmic domain of the alpha(1) subunit (X2C1), or alpha(2) cDNA truncated after the GFFKR sequence (X2C0). The X2C2 and X2C1 transfectants effectively adhered, spread, and formed focal adhesion complexes on type I collagen matrices. The X2C0 transfectants were less adherent to low concen trations of type I collagen, spread less well, and formed poorly defined fo cal adhesion complexes in comparison to the X2C2 and X2C1 transfectants. Th e X2C2 and X2C1 transfectants but not the X2C0 transfectants proliferated o n collagen substrates, Only the X2C2 transfectants developed elongate branc hes and tubules in three-dimensional collagen gels and migrated on type I c ollagen. These findings suggest a unique role for the in alpha(2) integrin cytoplasmic domain in postligand binding events and cooperative interaction s with growth factors that mediate epithelial differentiation and branching morphogenesis, Either intact alpha(1) or alpha(2) integrin subunit cytopla smic domain can promote cell cycle progression.