A POINT MUTATION OF INTEGRIN BETA-1 SUBUNIT BLOCKS BINDING OF ALPHA-5-BETA-1 TO FIBRONECTIN AND INVASIN BUT NOT RECRUITMENT TO ADHESION PLAQUES

A point mutation in a highly conserved region of the beta1 subunit, Asp130 to Ala (D130A) substitution, abrogates the Arg-Gly-Asp (RGD)-dependent binding of alpha5beta1 to fibronectin (FN) without disrupting gross structure or heterodimer assembly. The D130A mutation also interferes with binding to invasin, a ligand that lacks RGD sequence. In spite of the lack of detectable FN binding by alpha5beta1(D130A), it was recruited to adhesion plaques formed on FN by endogenous hamster receptors. Thus, intact ligand binding function is not required for recruitment of alpha5beta1 to adhesion plaques. Overexpression of beta1(D130A) partially interfered with endogenous alpha5beta1 function, thus defining a dominant negative beta1 integrin mutation.