title: Anopheles gambiae SRPN2 facilitates midgut invasion by the malaria parasite Plasmodium berghei.
abstract: We report on a phylogenetic and functional analysis of genes encoding three mosquito serpins (SRPN1, SRPN2 and SRPN3), which resemble known inhibitors of prophenoloxidase-activating enzymes in other insects. Following RNA interference induction by double-stranded RNA injection, knockdown of SRPN2 in adult Anopheles gambiae produced a notable phenotype: the appearance of melanotic pseudotumours, which increased in size and number with time, indicating spontaneous melanization and association with an observed lifespan reduction. Furthermore, knockdown of SRPN2 strongly interfered with the invasion of A. gambiae midguts by the rodent malaria parasite Plasmodium berghei. It did not affect ookinete formation, but markedly reduced oocyst numbers, by 97%, as a result of increased ookinete lysis and melanization.
authors.affiliation: Department of Biological Sciences, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Michel
authors.forename: Aidan
authors.initials: A
authors.lastname: Budd
authors.forename: Sofia
authors.initials: S
authors.lastname: Pinto
authors.forename: Toby J
authors.initials: TJ
authors.lastname: Gibson
authors.forename: Fotis C
authors.initials: FC
authors.lastname: Kafatos
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000852:Anopheles / Q000235:genetics / Q000469:parasitology*; D001499:Bayes Theorem; D015153:Blotting, Western; D018076:DNA, Complementary / Q000235:genetics; D041981:Gastrointestinal Tract / Q000469:parasitology*; D006790:Host-Parasite Interactions; D007150:Immunohistochemistry; D008136:Longevity; D008543:Melanins / Q000378:metabolism; D018613:Microscopy, Confocal; D008957:Models, Genetic; D008969:Molecular Sequence Data; D033661:Oocysts / Q000378:metabolism; D010641:Phenotype; D010802:Phylogeny; D010962:Plasmodium berghei / Q000502:physiology*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D015843:Serpins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D018076:DNA, Complementary; D008543:Melanins; D015843:Serpins