RGD-independent binding of integrin alpha9beta1 to the ADAM-12 and -15 disintegrin domains mediates cell-cell interaction.
ADAMs (a disintegrin and metalloproteases) mediate several important processes (e.g. tumor necrosis factor-alpha release, fertilization, and myoblast fusion). The ADAM disintegrin domains generally lack RGD motifs, and their receptors are virtually unknown. Here we show that integrin alpha(9)beta(1) specifically interacts with the recombinant ADAMs-12 and -15 disintegrin domains in an RGD-independent manner. We also show that interaction between ADAM-12 or -15 and alpha(9)beta(1) supports cell-cell interaction. Interestingly, the cation requirement and integrin activation status required for alpha(9)beta(1)/ADAM-mediated cell adhesion and cell-cell interaction is similar to those required for known integrin-extracellular matrix interaction. These results are quite different from recent reports that ADAM-2/alpha(6)beta(1) interaction during sperm/egg fusion requires an integrin activation status distinct from that for extracellular matrix interaction. These results suggest that alpha(9)beta(1) may be a major receptor for ADAMs that lack RGD motifs, and that, considering a wide distribution of ADAMs and alpha(9)beta(1), this interaction may be of potential biological and pathological significance.
Eto
K
K
Department of Vascular Biology, Scripps Research Institute, La Jolla, California 92037, USA.
Puzon-McLaughlin
W
W
Sheppard
D
D
Sehara-Fujisawa
A
A
Zhang
X P
XP
Takada
Y
Y
D051722:ADAM Proteins; D000072199:ADAM12 Protein; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D002412:Cations; D002448:Cell Adhesion; D002450:Cell Communication; D006224:Cricetinae; D018076:DNA, Complementary / Q000378:metabolism; D019483:Disintegrins / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D020014:K562 Cells; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism; D008345:Manganese / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009842:Oligopeptides / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D002412:Cations; D018076:DNA, Complementary; D019483:Disintegrins; D016023:Integrins; D008565:Membrane Proteins; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; C113256:integrin alpha 9 beta 1; D008345:Manganese; C047981:arginyl-glycyl-aspartic acid; D004492:Edetic Acid; D005982:Glutathione Transferase; D051722:ADAM Proteins; D000072199:ADAM12 Protein; C000606480:ADAM12 protein, human; C098660:ADAM15 protein, human; C490902:Adam15 protein, mouse; D008666:Metalloendopeptidases; D008274:Magnesium; D002118:Calcium