title: The CLIP-domain serine protease homolog SPCLIP1 regulates complement recruitment to microbial surfaces in the malaria mosquito Anopheles gambiae.
abstract: The complement C3-like protein TEP1 of the mosquito Anopheles gambiae is required for defense against malaria parasites and bacteria. Two forms of TEP1 are present in the mosquito hemolymph, the full-length TEP1-F and the proteolytically processed TEP1(cut) that is part of a complex including the leucine-rich repeat proteins LRIM1 and APL1C. Here we show that the non-catalytic serine protease SPCLIP1 is a key regulator of the complement-like pathway. SPCLIP1 is required for accumulation of TEP1 on microbial surfaces, a reaction that leads to lysis of malaria parasites or triggers activation of a cascade culminating with melanization of malaria parasites and bacteria. We also demonstrate that the two forms of TEP1 have distinct roles in the complement-like pathway and provide the first evidence for a complement convertase-like cascade in insects analogous to that in vertebrates. Our findings establish that core principles of complement activation are conserved throughout the evolution of animals.
authors.affiliation: Department of Life Sciences, Imperial College London, London, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Povelones
authors.forename: Lavanya
authors.initials: L
authors.lastname: Bhagavatula
authors.forename: Hassan
authors.initials: H
authors.lastname: Yassine
authors.forename: Lee Aun
authors.initials: LA
authors.lastname: Tan
authors.forename: Leanna M
authors.initials: LM
authors.lastname: Upton
authors.forename: Mike A
authors.initials: MA
authors.lastname: Osta
authors.forename: George K
authors.initials: GK
authors.lastname: Christophides
mesh_terms: D000818:Animals; D000852:Anopheles / Q000201:enzymology* / Q000235:genetics / Q000469:parasitology; D003167:Complement Activation; D003165:Complement System Proteins / Q000235:genetics / Q000378:metabolism*; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D057057:Serine Proteases / Q000235:genetics / Q000378:metabolism*
chemical_list: D019476:Insect Proteins; C544265:TEP1 protein, Anopheles gambiae; D003165:Complement System Proteins; D057057:Serine Proteases
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