Cutting edge: inhibiting measles virus infection but promoting reproduction: an explanation for splicing and tissue-specific expression of CD46.
Membrane cofactor protein (MCP; CD46) regulates the complement cascade by inhibiting C3b and C4b deposited on self tissue. This function resides in the complement control protein repeats (CCPs), with CCPs 2-4 essential for regulation. MCP is expressed on the inner acrosomal membrane of human sperm, and Abs to CCP1 inhibit sperm-egg interactions. In somatic tissues, New World monkeys express an alternatively spliced form of MCP lacking CCP1. Although retaining complement-regulatory activity, this form is postulated to render these species less susceptible to strains of the measles virus whose hemagglutinin requires CCP1 and CCP2 for attachment. Using PCR, sequencing, Western blotting, and immunohistochemistry, we characterized MCP expression in the testes and sperm of two New World monkeys. In these species, sperm express MCP bearing CCP1. The germ cell-specific expression pattern of this domain strongly suggests an evolutionarily conserved role for MCP in fertilization.
Riley
Rebecca C
RC
Division of Rheumatology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Tannenbaum
Pamela L
PL
Abbott
David H
DH
Atkinson
John P
JP
D020101:Acrosome Reaction / Q000276:immunology*; D017398:Alternative Splicing / Q000276:immunology*; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D002144:Callithrix; D002236:Carbohydrate Conformation; D004591:Electrophoresis, Polyacrylamide Gel; D006031:Glycosylation; D006801:Humans; D007425:Intracellular Membranes / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008457:Measles / Q000235:genetics / Q000276:immunology / Q000503:physiopathology* / Q000517:prevention & control*; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D011991:Receptors, Virus / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D020449:Repetitive Sequences, Amino Acid; D012453:Saimiri; D013094:Spermatozoa / Q000737:chemistry / Q000378:metabolism; D013737:Testis / Q000737:chemistry / Q000378:metabolism; D014764:Viral Proteins / Q000032:analysis / Q000235:genetics
D015703:Antigens, CD; C497857:CD46 protein, human; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011991:Receptors, Virus; D014764:Viral Proteins; C074554:herpesvirus saimiri protein, Saimiriine herpesvirus 2