Original Article

The Short Arm of the Laminin 2 Chain Plays a Pivotal Role in the Incorporation of Laminin 5 into the Extracellular Matrix and in Cell Adhesion

Correspondence to: Guerrino Meneguzzi, U385 INSERM, Faculté de Médecine, Cedex 2, 06107 Nice, France. Tel:(33) 493-37-77-78 Fax:(33) 493-81-14-04 E-mail:meneguzz{at}unice.fr.

Laminin 5 is a basement membrane component that actively promotes adhesion and migration of epithelial cells. Laminin 5 undergoes extracellular proteolysis of the 2 chain that removes the NH₂-terminal short arm of the polypeptide and reduces the size of laminin 5 from 440 to 400 kD. The functional consequence of this event remains obscure, although lines of evidence indicate that cleavage of the 2 chain potently stimulated scattering and migration of keratinocytes and cancer cells. To define the biological role of the 2 chain short arm, we expressed mutated 2 cDNAs into immortalized 2-null keratinocytes. By immunofluorescence and immunohistochemical studies, cell detachment, and adhesion assays, we found that the 2 short arm drives deposition of laminin 5 into the extracellular matrix (ECM) and sustains cell adhesion. Our results demonstrate that the unprocessed 440-kD form of laminin 5 is a biologically active adhesion ligand, and that the 2 globular domain IV is involved in intermolecular interactions that mediate integration of laminin 5 in the ECM and cell attachment.

Key Words: keratinocyte, epithelial adhesion, cell migration, basement membrane, epidermolysis bullosa

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