Laminin isoforms containing the gamma 3 chain are unable to bind to integrins due to the absence of the glutamic acid residue conserved in the C-terminal regions of the gamma 1 and gamma 2 chains

[摘要]：Laminins are the major cell adhesive proteins in basement membranes, and consist of three subunits termed alpha, beta, and gamma. Recently, we found that the Glu residue at the third position from the C termini of the gamma 1 and gamma 2 chains is critically involved in integrin binding by laminins. However, the gamma 3 chain lacks this Glu residue, suggesting that laminin isoforms containing the gamma 3 chain may be unable to bind to integrins. To address this possibility, we expressed the E8 fragment of laminin-213 and found that it was incapable of binding to integrins. Similarly, the E8 fragment of laminin-113 was expressed and also found to be inactive in binding to integrins, confirming the distinction between the integrin binding activities of gamma 3 chain-containing isoforms and those containing the gamma 1 or gamma 2 chain. To further address the importance of the Glu residue, we swapped the C-terminal four amino acids of the gamma 3 chain with the C-terminal nine amino acids of the gamma 1 chain, which contain the Glu residue. The resulting chimeric E8 fragment of laminin-213 became fully active in integrin binding, whereas replacement with the nine amino acids of the gamma 1 chain after substitution of Gln for the conserved Glu residue failed to restore the integrin binding activity. These results provide both loss-of-function and gain-of-function evidence that laminin isoforms containing the gamma 3 chain are unable to bind to integrins due to the absence of the conserved Glu residue, which should play a critical role in integrin binding by laminins.

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