Mechanisms of basement membrane recognition by cell with special reference to cell adhesion-dependent signal transduction

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Roles of individual subunit chains of laminins (i.e., alpha, beta and gamma chains) in integrin binding by laminins have been investigated. We demonstrated that the C-terminal region of the gamma1 and gamma2 chains, particularly the Glu residue at the third position from their C-termini, was critically involved in integrin recognition of laminins. Thus, the deletion of the Glu residue or the substitution of a Gln for the Glu residue abrogated the integrin binding activity of laminin isoforms containing either gamma1 or gamma2 chains. To extend the importance of the Glu residue within the gamma1 and gamma2 chains, we also demonstrated that the gamma3 chain that is shorter than other gamma chains and lacks the Glu residue was defective in binding to cognitive integrins. We also found that the C-terminal regions of the beta chains, particularly the C-terminal 22 amino acid residues, were involved in modulation of integrin binding affinities of laminins. Thus, the isoforms containing the beta2 chain was more potent than those containing the beta1 chain in binding to cognitive integrins, e.g., alpha3beta1. These results indicate that the C-terminal regions of both beta and gamma chains participate in the integrin binding by laminins. We also demonstrated that among the eight RGD-binding integrins, alpha8beta1 bound specifically to nephronectin.