The metallo-disintegrin ADAM10 (MADM) from bovine kidney has type IV collagenase activity in vitro

The metallo-disintegrins (ADAMs) are a family of mammalian proteins with significant amino acid sequence identity and a domain organisation similar to the snake venom metalloproteinases (reprolysins). They have been implicated in a wide variety of processes such as cell-cell and cell matrix adhesion and proteolysis of the extracellular matrix in a wide variety of cell types. They may also be involved in events such as the processing of plasma membrane proteins, proteolysis in the secretory pathway and pro-cytokine conversion processes. Due to the close relationship of the ADAM proteins with snake venom enzymes which have been demonstrated to be type IV collagenases, we investigated whether purified bovine ADAM10 could cleave basement membrane type IV collagen. We show here that ADAM10 purified from bovine kidney can cleave a basement membrane collagen type IV preparation as assessed by SDS-PAGE analysis and novel epitope recognition with a specific antibody to type IV collagen. The demonstration that a metallo-disintegrin displays a type IV collagenase activity may be relevant to tumour metastasis and may have general relevance to extracellular re-modeling in renal pathology and a variety of other pathological states where compromise of the basement membrane is involved.