Regulation of Cell Adhesion and Type VII Collagen Binding by the β3 Chain Short Arm of Laminin-5: Effect of Its Proteolytic Cleavage

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Abstract
The basement membrane protein laminin-5 (Lm5), a heterotrimer of α3 (or α3A), β3, and γ2 chains, regulates cellular adhesion and motility. Here we examined the proteolysis and biological function of the laminin β3 chain. First, we found that the β3 chain of Lm5 is cleaved at its N-terminal, short arm by an endogenous proteinase(s) in normal human keratinocytes and some other cell lines. To examine the effect of β3 chain cleavage, we expressed a wild-type Lm5 and two Lm5 mutants with partially deleted β3 chains in HEK293 cells. Experiments with the purified Lm5 forms demonstrated that the deletion of the β3 short arm or its N-terminal domain LN decreases the cell adhesion activity of Lm5, but does not significantly affect the motility activity. A recombinant β3 short arm protein enhanced integrin-mediated cell adhesion to Lm5 by binding to an unidentified cell receptor. It was also found that the laminin EGF-like domain of the β3 short arm is a binding site for type VII collagen. These results suggest that the β3 short arm is involved not only in the matrix assembly of Lm5, but also in its cell adhesion activity. The proteolytic cleavage of the β3 chain may modulate these functions of Lm5 in vivo.