Interaction between the cytodomains of the α3 and β1 integrin subunits regulates remodelling of adhesion complexes on laminin

The first step of laminin 1-induced signal transduction is initiated by the formation of α6β1 integrin-specific adhesion complexes. In contrast, on other laminin isoforms the adhesion complexes are α3β1 integrin-specific due to a transdominant regulation of the α6β1 integrin by the α3β1 integrin. To determine the mechanism of this regulation, peptides representing the cytoplasmic domain of the α3 or α6 integrin subunits were microinjected together with recombinant enhanced green fluorescence protein into live fibroblasts. Microinjection of the α3 integrin peptide to laminin 1-adherent cells displaying α6β1 integrin-specific adhesion complexes resulted in the disengagement of the α6β1 integrin, while microinjection of green fluorescence protein alone or in combination with the α6 integrin cytodomain had no effect. Further surface plasmon resonance studies revealed that the cytodomain of the β1 integrin subunit interacts with low affinity with the cytoplasmic tail of the α3 integrin subunit, but not with that of several other a subunits including α6. These results imply that the cytoplasmic tails of the integrin α subunits play a critical role in the regulation of integrin-induced signal transduction. In particular, the intracellular tail of the α3 integrin subunit controls the formation of adhesion complexes in cells adhering to laminins.