Leucine-rich repeat protein complex activates mosquito complement in defense against Plasmodium parasites.
Leucine-rich repeat-containing proteins are central to host defense in plants and animals. We show that in the mosquito Anopheles gambiae, two such proteins that antagonize malaria parasite infections, LRIM1 and APL1C, circulate in the hemolymph as a high-molecular-weight complex held together by disulfide bridges. The complex interacts with the complement C3-like protein, TEP1, promoting its cleavage or stabilization and its subsequent localization on the surface of midgut-invading Plasmodium berghei parasites, targeting them for destruction. LRIM1 and APL1C are members of a protein family with orthologs in other disease vector mosquitoes and appear to be important effectors in innate mosquito defenses against human pathogens.
Povelones
Michael
M
Division of Cell and Molecular Biology, Department of Life Sciences, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
Waterhouse
Robert M
RM
Kafatos
Fotis C
FC
Christophides
George K
GK
D020816:Amino Acid Motifs; D000818:Animals; D000852:Anopheles / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology*; D003167:Complement Activation; D003176:Complement C3 / Q000276:immunology / Q000378:metabolism; D004064:Digestive System / Q000469:parasitology; D005260:Female; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D017344:Genes, Insect; D006458:Hemolymph; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D007303:Insect Vectors / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D007930:Leucine / Q000737:chemistry; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D010962:Plasmodium berghei / Q000276:immunology* / Q000502:physiology
D003176:Complement C3; D019476:Insect Proteins; C540280:LRIM1 protein, Anopheles gambiae; D046912:Multiprotein Complexes; D007930:Leucine