title: Emerging roles and new functions of CD46.
abstract: In the past 20 years, our understanding of the workings of complement regulatory protein, CD46 (membrane cofactor protein), has grown as has the impressive list of pathogens interacting with this membrane-bound complement inhibitor. Referred to as a "pathogen magnet," CD46 serves as a receptor for seven human pathogens. Initially discovered as a widely expressed C3b- and C4b-binding protein, it was subsequently shown to be a cofactor for the serine protease factor I to inactivate by limited proteolysis these two opsonins and components of the convertases. The involvement of CD46 in reproductive processes continues to be an emerging story. It is a protector of placental tissue, but it may also play a more direct role in reproduction through its expression on the inner acrosomal membrane of spermatozoa. Cross-linking CD46 with antibodies or natural or pathogenic ligands induces rapid turnover and signaling events. In this regard, much attention is currently focused on generating human T lymphocyte regulatory cells by cross-linking CD46. Finally, highlighting its importance in protecting cells against excessive complement activation is the discovery that even a heterozygous deficiency of CD46 predisposes to hemolytic uremic syndrome.
authors.affiliation: Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8045, St. Louis, MO 63110, USA.
authors.forename: M Kathryn
authors.initials: MK
authors.lastname: Liszewski
authors.forename: Claudia
authors.initials: C
authors.lastname: Kemper
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Price
authors.forename: John P
authors.initials: JP
authors.lastname: Atkinson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003167:Complement Activation; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D051916:Membrane Cofactor Protein / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011247:Pregnancy; D011991:Receptors, Virus / Q000276:immunology; D012098:Reproduction / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: C497857:CD46 protein, human; D051916:Membrane Cofactor Protein; D011991:Receptors, Virus