Secretion of active membrane type 1 matrix metalloproteinase (MMP-14) into extracellular space in microvesicular exosomes.

Membrane type 1 matrix metalloproteinase (MT1-MMP, MMP14) is an efficient extracellular matrix (ECM) degrading enzyme that plays important roles in tissue homeostasis and cell invasion. Like a number of type I membrane proteins, MT1-MMP can be internalized from the cell surface through early and recycling endosomes to late endosomes, and recycled to the plasma membrane. Late endosomes participate in the biogenesis of small (30-100 nm) vesicles, exosomes, which redirect plasma membrane proteins for extracellular secretion.

ADAM10-mediated release of complement membrane cofactor protein during apoptosis of epithelial cells.

Membrane cofactor protein CD46 controls complement activation on cells, is a receptor for several pathogens, and modulates immune responses by affecting CD8(+) T cells. Cells can release CD46 in an intact form on membrane vesicles and in a truncated form by a metalloproteolytic cleavage. The mechanism of shedding and its relationship to cell physiology has remained unclear.

Complement inhibitor membrane cofactor protein (MCP; CD46) is constitutively shed from cancer cell membranes in vesicles and converted by a metalloproteinase to a functionally active soluble form.

Human cell-surface protein CD46 protects cells from complement damage, regulates immune functions through signaling and acts as a receptor for certain pathogenic microbes. Multiple molecular weight isoforms of membrane bound CD46 are produced by alternative splicing of the CD46 mRNA in an area coding for the serine/threonine/proline-rich region or for the cytoplasmic tail. We demonstrate that CD46 becomes proteolytically modified on cell membranes.