title: Diverged alleles of the Anopheles gambiae leucine-rich repeat gene APL1A display distinct protective profiles against Plasmodium falciparum.
abstract: Functional studies have demonstrated a role for the Anopheles gambiae APL1A gene in resistance against the human malaria parasite, Plasmodium falciparum. Here, we exhaustively characterize the structure of the APL1 locus and show that three structurally different APL1A alleles segregate in the Ngousso colony. Genetic association combined with RNAi-mediated gene silencing revealed that APL1A alleles display distinct protective profiles against P. falciparum. One APL1A allele is sufficient to explain the protective phenotype of APL1A observed in silencing experiments. Epitope-tagged APL1A isoforms expressed in an in vitro hemocyte-like cell system showed that under assay conditions, the most protective APL1A isoform (APL1A(2)) localizes within large cytoplasmic vesicles, is not constitutively secreted, and forms only one protein complex, while a less protective isoform (APL1A(1)) is constitutively secreted in at least two protein complexes. The tested alleles are identical to natural variants in the wild A. gambiae population, suggesting that APL1A genetic variation could be a factor underlying natural heterogeneity of vector susceptibility to P. falciparum.
authors.affiliation: Unit of Insect Vector Genetics and Genomics, Department of Parasitology and Mycology, CNRS Unit URA 3012, Institut Pasteur, Paris, France.
authors.forename: Inge
authors.initials: I
authors.lastname: Holm
authors.forename: Catherine
authors.initials: C
authors.lastname: Lavazec
authors.forename: Thierry
authors.initials: T
authors.lastname: Garnier
authors.forename: Christian
authors.initials: C
authors.lastname: Mitri
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Riehle
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bischoff
authors.forename: Emma
authors.initials: E
authors.lastname: Brito-Fravallo
authors.forename: Eizo
authors.initials: E
authors.lastname: Takashima
authors.forename: Isabelle
authors.initials: I
authors.lastname: Thiery
authors.forename: Agnes
authors.initials: A
authors.lastname: Zettor
authors.forename: Stephane
authors.initials: S
authors.lastname: Petres
authors.forename: Catherine
authors.initials: C
authors.lastname: Bourgouin
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Vernick
authors.forename: Karin
authors.initials: K
authors.lastname: Eiglmeier
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D000852:Anopheles / Q000235:genetics* / Q000276:immunology / Q000469:parasitology; D023061:Gene Order; D020868:Gene Silencing; D017344:Genes, Insect; D006239:Haplotypes; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000276:immunology; D021381:Protein Transport; D040641:Quantitative Trait Loci; D016415:Sequence Alignment