Meltrin gamma(ADAM-9) mediates cellular adhesion through alpha(6)beta(1 )integrin, leading to a marked induction of fibroblast cell motility.
The ADAMs (A Disintegrin and Metalloprotease Domains) are a family of membrane-anchored proteins that play a role in fertilisation, myoblast fusion and ectodomain shedding of cell surface proteins. Meltrin gamma (ADAM-9) is a widely expressed member of this family and is involved in the shedding of heparin binding epidermal growth factor. Here we report that meltrin gamma can function as a cell adhesion molecule via its disintegrin domain. Using solid-phase binding assays and antibody inhibition experiments, we demonstrate that a murine meltrin gamma-Fc (Mel gamma -Fc) fusion protein binds to the integrin alpha(6)beta(1) on the surface of fibroblast cell lines, HT1080 and Wehi 164 in a specific manner. Since alpha(6)beta(1) is important for the motility of several cell types on laminin, cell migration studies using time-lapse video microscopy were performed. Cells adhering to Mel gamma-Fc displayed a rounded morphology and a marked increase (eight- to tenfold) in their motility compared to that on laminin. Furthermore, the p160 ROCK kinase inhibitor Y-27632 specifically reduced the migration of cells on meltrin gamma but had no effect on migration of cells on laminin, whilst the general tyrosine phoshorylation inhibitor, genistein, inhibited cell migration on both substrates. These results together suggest that meltrin gamma may play a role in regulating the motility of cells by binding to alpha(6)beta(1) integrin and this may be important during a variety of biological and pathological processes.
Nath
D
D
School of Biological Sciences, University of East Anglia, Norwich, NR4 7TJ, UK.
Slocombe
P M
PM
Webster
A
A
Stephens
P E
PE
Docherty
A J
AJ
Murphy
G
G
D051722:ADAM Proteins; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D019483:Disintegrins; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology*; D007141:Immunoglobulin Fc Fragments; D039121:Integrin alpha6beta1; D016023:Integrins / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology*; D008666:Metalloendopeptidases; D051379:Mice; D009124:Muscle Proteins / Q000502:physiology*; D011993:Recombinant Fusion Proteins
D019483:Disintegrins; D007141:Immunoglobulin Fc Fragments; D039121:Integrin alpha6beta1; D016023:Integrins; D008565:Membrane Proteins; D009124:Muscle Proteins; D011993:Recombinant Fusion Proteins; D051722:ADAM Proteins; C498316:Adam9 protein, mouse; D008666:Metalloendopeptidases