RGD-independent Binding of Integrin α9β1 to the ADAM-12 and -15 Disintegrin Domains Mediates Cell-Cell Interaction*

By K. Eto, W. Puzon‐McLaughlin, D. Sheppard, A. Sehara-Fujisawa, Xi-ping Zhang, Y. Takada. Journal of Biological Chemistry, 2000

210 citations recorded by the source corpus.

ADAMs (a disintegrinand metalloproteases) mediate several important processes (e.g. tumor necrosis factor-α release, fertilization, and myoblast fusion). The ADAM disintegrin domains generally lack RGD motifs, and their receptors are virtually unknown. Here we show that integrin α9β1specifically 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 α9β1supports cell-cell interaction. Interestingly, the cation requirement and integrin activation status required for α9β1/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/α6β1 interaction during sperm/egg fusion requires an integrin activation status distinct from that for extracellular matrix interaction. These results suggest that α9β1 may be a major receptor for ADAMs that lack RGD motifs, and that, considering a wide distribution of ADAMs and α9β1, this interaction may be of potential biological and pathological significance.

Subfields: Cell Biology, Immunology and Allergy, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/940c0e0b368d8591ceef15908f1333a759ccd15d

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Citations in the corpus

• Positive selection at reproductive ADAM genes with potential intercellular binding activity. (2004, background): “…tissue (Sagane et al. 1999); ADAMs 9, 12, and 15, genes with adhesion roles in fibroblasts, myoblasts and haemopoietic cells (Nath et al.1999, 2000; Eto et al. 2000); and ADAMs 7 and 18, genes expressed in the epididymis with roles in sperm development (Cornwall and Hsia 1997; Frayne, Hurd, and…”
• Recombinant disintegrin domain of ADAM15 inhibits the proliferation and migration of Bel-7402 cells. (2013, background): “The integrin-binding domain of rhddADAM15 is thought to be key for its inhibition in metastasis [12,13,24].”
• The ADAMs family of metalloproteases: multidomain proteins with multiple functions. (2003, background): “ADAMs do associate with tumor cell surfaces: ADAM12 and ADAM15 bind to 9 1-expressing Ntera-2 embryonic carcinoma cells (Eto et al. 2000); ADAM15 binds to v 3 expressing melanoma cells (Zhang et al.”
• Phenotypic Analysis of Meltrin α (ADAM12)-Deficient Mice: Involvement of Meltrin α in Adipogenesis and Myogenesis (2003, background): “Other studies suggest that ADAMs are also involved in cell-cell or cell-extracellular matrix interactions through their interaction with integrins (6, 10 , 27, 48) or proteoglycans (15).”
• A Disintegrin and Metalloprotease (ADAM): Historical Overview of Their Functions (2016, background): “However, human ADAM‐15 can also bind integrin in a RGD‐independent manner as shown for the binding of α9β1 integrin [15].”