Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Motifs
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Animals
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Anopheles / genetics
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Anopheles / immunology*
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Anopheles / metabolism
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Anopheles / parasitology*
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Complement Activation*
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Complement C3 / immunology
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Complement C3 / metabolism
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Digestive System / parasitology
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Female
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Gene Knockdown Techniques
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Gene Silencing
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Genes, Insect
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Hemolymph
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Insect Proteins / chemistry
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Insect Proteins / genetics
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Insect Proteins / isolation & purification
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Insect Proteins / metabolism*
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Insect Vectors / genetics
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Insect Vectors / immunology
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Insect Vectors / metabolism
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Insect Vectors / parasitology
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Leucine / chemistry
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Multiprotein Complexes / chemistry
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Multiprotein Complexes / metabolism
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Plasmodium berghei / immunology*
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Plasmodium berghei / physiology
Substances
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Complement C3
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Insect Proteins
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LRIM1 protein, Anopheles gambiae
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Multiprotein Complexes
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Leucine