Diverged alleles of the Anopheles gambiae leucine-rich repeat gene APL1A display distinct protective profiles against Plasmodium falciparum. PLoS One 2012;7(12):e52684
Date
01/04/2013Pubmed ID
23285147Pubmed Central ID
PMC3532451DOI
10.1371/journal.pone.0052684Scopus ID
2-s2.0-84871695278 (requires institutional sign-in at Scopus site) 11 CitationsAbstract
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.
Author List
Holm I, Lavazec C, Garnier T, Mitri C, Riehle MM, Bischoff E, Brito-Fravallo E, Takashima E, Thiery I, Zettor A, Petres S, Bourgouin C, Vernick KD, Eiglmeier KAuthor
Michelle M. Riehle PhD Assistant Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AllelesAmino Acid Sequence
Animals
Anopheles
Gene Order
Gene Silencing
Genes, Insect
Haplotypes
Molecular Sequence Data
Plasmodium falciparum
Protein Transport
Quantitative Trait Loci
Sequence Alignment