Leucine-rich repeat protein complex activates mosquito complement in defense against Plasmodium parasites.

Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 0404511 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-9203 (Electronic) Linking ISSN: 00368075 NLM ISO Abbreviation: Science Subsets: MEDLINE

Publication: : Washington, DC : American Association for the Advancement of Science
Original Publication: New York, N.Y. : [s.n.] 1880-

Complement Activation*; Anopheles/*immunology ; Anopheles/*parasitology ; Insect Proteins/*metabolism ; Plasmodium berghei/*immunology; Amino Acid Motifs ; Animals ; Anopheles/genetics ; Anopheles/metabolism ; Complement C3/immunology ; Complement C3/metabolism ; Digestive System/parasitology ; Female ; Gene Knockdown Techniques ; Gene Silencing ; Genes, Insect ; Hemolymph ; Insect Proteins/chemistry ; Insect Proteins/genetics ; Insect Proteins/isolation & purification ; Insect Vectors/genetics ; Insect Vectors/immunology ; Insect Vectors/metabolism ; Insect Vectors/parasitology ; Leucine/chemistry ; Multiprotein Complexes/chemistry ; Multiprotein Complexes/metabolism ; Plasmodium berghei/physiology

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.

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GR077229/Z/05/Z United Kingdom WT_ Wellcome Trust; 077229 United Kingdom WT_ Wellcome Trust; P01 AI044220 United States AI NIAID NIH HHS; BB/C519670/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council; 2P01AI044220-06A1 United States AI NIAID NIH HHS; United Kingdom WT_ Wellcome Trust; BB/E002641/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council; 069962 United Kingdom WT_ Wellcome Trust

Indexing Agency: NLM Local ID #: UKMS28183.

0 (Complement C3)
0 (Insect Proteins)
0 (LRIM1 protein, Anopheles gambiae)
0 (Multiprotein Complexes)
GMW67QNF9C (Leucine)

Date Created: 20090307 Date Completed: 20090501 Latest Revision: 20240519

20250114

PMC2790318

10.1126/science.1171400

19264986