The short arm of the laminin gamma2 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 proteolysis of the gamma2 chain that removes the NH(2)-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 gamma2 chain potently stimulated scattering and migration of keratinocytes and cancer cells. To define the biological role of the gamma2 chain short arm, we expressed mutated gamma2 cDNAs into immortalized gamma2-null keratinocytes. By immunofluorescence and immunohistochemical studies, cell detachment, and adhesion assays, we found that the gamma2 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 gamma2 globular domain IV is involved in intermolecular interactions that mediate integration of laminin 5 in the ECM and cell attachment.
Gagnoux-Palacios
L
L
Faculty of Medicine, U385 Institut National de la Santé et de la Recherche Médicale, Cedex 2, 06107 Nice, France.
Allegra
M
M
Spirito
F
F
Pommeret
O
O
Romero
C
C
Ortonne
J P
JP
Meneguzzi
G
G
D001485:Basement Membrane / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D002448:Cell Adhesion / Q000502:physiology; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000502:physiology; D017931:DNA Primers; D018076:DNA, Complementary; D004820:Epidermolysis Bullosa / Q000378:metabolism / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism*; D007797:Laminin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed / Q000502:physiology; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D017931:DNA Primers; D018076:DNA, Complementary; D016326:Extracellular Matrix Proteins; C400567:LAMC2 protein, human; D007797:Laminin; C097043:laminin alpha5