title: A mosquito-specific protein family includes candidate receptors for malaria sporozoite invasion of salivary glands.
abstract: We describe a previously unrecognized protein family from Aedes and Anopheles mosquitoes, here named SGS proteins. There are no SGS homologues in Drosophila or other eukaryotes, but SGS presence in two mosquito genera suggests that the protein family is widespread among mosquitoes. Ae. aegypti aaSGS1 mRNA and protein are salivary gland specific, and protein is localized in the basal lamina covering the anatomical regions that are preferentially invaded by malaria sporozoites. Anti-aaSGS1 antibodies inhibited sporozoite invasion into the salivary glands in vivo, confirming aaSGS1 as a candidate sporozoite receptor. By homology to aaSGS1 we identified the complete complement of four SGS genes in An. gambiae, which were not recognized in the genome annotation. Two An. gambiae SGS genes display salivary gland specific expression like aaSGS1. Bioinformatic analysis predicts that SGS proteins possess heparin-binding domains, and have among the highest density of tyrosine sulphation sites of all An. gambiae proteins. The major sporozoite surface proteins (CS and TRAP) also bind heparin, and interact with sulphoconjugates during liver cell invasion. Thus, we speculate that sporozoite invasion of mosquito salivary glands and subsequently the vertebrate liver may share similar mechanisms based on sulphation. Phylogenomic analysis suggests that an SGS ancestor was involved in a lateral gene transfer.
authors.affiliation: Center for Microbial and Plant Genomics, and Department of Microbiology, University of Minnesota, St Paul, MN 55108, USA.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Korochkina
authors.forename: Catherine
authors.initials: C
authors.lastname: Barreau
authors.forename: Gabriele
authors.initials: G
authors.lastname: Pradel
authors.forename: Erin
authors.initials: E
authors.lastname: Jeffery
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Ramya
authors.initials: R
authors.lastname: Natarajan
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Shabanowitz
authors.forename: Donald
authors.initials: D
authors.lastname: Hunt
authors.forename: Ute
authors.initials: U
authors.lastname: Frevert
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Vernick
mesh_terms: D000330:Aedes / Q000235:genetics / Q000378:metabolism* / Q000469:parasitology; D000595:Amino Acid Sequence; D000818:Animals; D000852:Anopheles / Q000235:genetics / Q000378:metabolism* / Q000469:parasitology; D000911:Antibodies, Monoclonal; D019476:Insect Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D010964:Plasmodium gallinaceum / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012469:Salivary Glands / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D012471:Salivary Proteins and Peptides / Q000378:metabolism*; D034101:Sporozoites / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D019476:Insect Proteins; D011956:Receptors, Cell Surface; D012471:Salivary Proteins and Peptides