Characterization and developmental gene regulation of a large gene family encoding amastin surface proteins in...

The ability of Leishmania amastigotes to survive within the drastic environmental changes encountered in the phagolysosomes of mammalian macrophages is heavily dependent on the developmental regulation of a variety of genes. The identification of genes that are expressed preferentially in the mammalian stage of the parasite should increase our understanding of the molecular mechanisms regulating stage-specific gene expression and of the determinants that control its intracellular survival and contribute to its pathogenesis. We report here detailed sequence characterization and structural organization of the amastin gene family in Leishmania major and Leishmania infantum and the study of their developmental gene regulation throughout the parasite's life cycle. Amastin surface proteins represent the largest developmentally regulated gene family reported so far in Leishmania comprising up to 45 members. All the members of the amastin gene family in both Leishmania and Trypanosoma species share a similar structural organization and contain a highly conserved 11 amino acid extracellular domain, which is unique to amastin proteins. The majority of the amastin gene homologs are specifically expressed in the amastigote stage of the parasite. Three distinct RNA elements were identified in the 3'-untranslated regions (3'UTR) of the amastin transcripts. The majority of these transcripts contain a conserved 450 nt cis-acting 3'UTR element shown previously to regulate stage-specific gene expression at the level of translation, which suggests that several amastin homologs may be regulated by a similar mechanism of translational control inside the macrophage. These findings further highlight the unique features of gene expression control in Leishmania.