Conserved role of a complement-like protein in phagocytosis revealed by dsRNA knockout in cultured cells of the mosquito, Anopheles gambiae.
We characterize a novel hemocyte-specific acute phase glycoprotein from the malaria vector, Anopheles gambiae. It shows substantial structural and functional similarities, including the highly conserved thioester motif, to both a central component of mammalian complement system, factor C3, and to a pan-protease inhibitor, alpha2-macroglobulin. Most importantly, this protein serves as a complement-like opsonin and promotes phagocytosis of some Gram-negative bacteria in a mosquito hemocyte-like cell line. Chemical inactivation by methylamine and depletion by double-stranded RNA knockout demonstrate that this function is dependent on the internal thioester bond. This evidence of a complement-like function in a protostome animal adds substantially to the accumulating evidence of a common ancestry of immune defenses in insects and vertebrates.
Levashina
E A
EA
EMBL, 1 Meyerhofstrasse, 69117, Heidelberg, Germany.
Moita
L F
LF
Blandin
S
S
Vriend
G
G
Lagueux
M
M
Kafatos
F C
FC
D000818:Animals; D000852:Anopheles / Q000276:immunology*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003176:Complement C3 / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D053938:DNA Fragmentation; D005260:Female; D006090:Gram-Negative Bacteria / Q000276:immunology; D006434:Hemocytes / Q000502:physiology; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D008969:Molecular Sequence Data; D009691:Nucleic Acid Denaturation; D010587:Phagocytosis / Q000276:immunology*; D017434:Protein Structure, Tertiary; D012330:RNA, Double-Stranded; D014158:Transcription, Genetic / Q000276:immunology; D000511:alpha-Macroglobulins / Q000235:genetics / Q000276:immunology
D003176:Complement C3; D019476:Insect Proteins; D012330:RNA, Double-Stranded; D000511:alpha-Macroglobulins