THE MEMBRANE-CYTOPLASM INTERFACE OF INTEGRIN ALPHA-SUBUNITS IS CRITICAL FOR RECEPTOR LATENCY

Localization of integrin receptors to focal contact sites occurs upon ligand binding. This activity is latent, since unoccupied integrin rec eptors do not localize to focal contacts. Deletion analysis has reveal ed that the alpha cytoplasmic domain is required for the maintenance o f integrin receptor latency. Our current hypothesis for the mechanism of integrin post-ligand binding events is that there is a change in re lationship of alpha and beta cytoplasmic domains, which overcomes rece ptor latency. One possible mechanism for such a change would involve t he amino acid residues at the membrane-cytoplasm interface. To test th is hypothesis, we have produced point mutations in the human integrin alpha(1) subunit. These mutations had no effect on the adhesion via al pha(1) beta(1) to its ligand, collagen IV. However, receptor latency i s lost in one of these mutants, leading to constitutive focal contact localization. This effect did not occur in receptors with an exchange of intracellular domains, suggesting that the mechanism of loss of lat ency involves a relative motion of the integrin chains. These results suggest a model in which post-ligand binding events in integrin recept ors are associated with changes in the position of the alpha and beta cytoplasmic domains.