Membrane Cofactor Protein

Since its discovery ~30 years ago, our knowledge about membrane cofactor protein (MCP; CD46) has expanded beyond its role as a potent complement regulator that is expressed as a family of four isoforms on most cells and that differ in O-glycosylation and cytoplasmic tails. Initially known as a cofactor for the factor-I-mediated cleavage of C3b and C4b, CD46 functions now include roles as a pathogen magnet, key constituent in human T cell biology, promoter of epithelial cell autophagy and player in reproductive biology. CD46 also is a promising new therapeutic target for xenotransplantation of transgenic CD46-expressing pig organs, for delivery of anti-tumour agents via viruses (especially adenovirus), and for cancer treatment regimens via use of CD46 monoclonal antibodies. Further, since mice primarily express CD46 on spermatozoa and in eye, the Cd46^-/- mice may assist CD46 reproductive studies and provide a much needed model to study age-related macular degeneration.