The short arm of the laminin gamma 2 chain plays a pivotal role in the incorporation of laminin 5 into the extracellular matrix and in cell adhesion

Laminin 5 is a basement membrane component that actively promotes adhesion and migration of epithelial cells. Laminin 5 undergoes extracellular proteo lysis of the gamma2 chain that removes the NH2-terminal short arm of the po lypeptide and reduces the size of laminin 5 from 440 to 400 kD. The functio nal consequence of this event remains obscure, although lines of evidence i ndicate that cleavage of the gamma2 chain potently stimulated scattering an d migration of keratinocytes and cancer cells. To define the biological rol e of the gamma2 chain short arm, we expressed mutated gamma2 cDNAs into imm ortalized gamma2-null keratinocytes. By immunofluorescence and immunohistoc hemical studies, cell detachment, and adhesion assays, we found that the y gamma short arm drives deposition of laminin 5 into the extracellular matri x (ECM) and sustains cell adhesion. Our results demonstrate that the unproc essed 440-kD form of laminin 5 is a biologically active adhesion ligand, an d that the gamma2 globular domain IV is involved in intermolecular interact ions that mediate integration of laminin 5 in the ECM and cell attachment.