Transcription factor AP2-Sp and its target genes in malarial sporozoites.

The malarial sporozoite is the stage that infects the liver, and genes expressed in this stage are potential targets for vaccine development. Here, we demonstrate that specific gene expression in this stage is regulated by an AP2-related transcription factor, designated AP2-Sp (APETALA2 in sporozoites), that is expressed from the late oocyst to the salivary gland sporozoite. Disruption of the AP2-Sp gene did not affect parasite replication in the erythrocyte but resulted in loss of sporozoite formation. The electrophoretic mobility-shift assay showed that the DNA-binding domain of AP2-Sp recognizes specific eight-base sequences, beginning with TGCATG, which are present in the proximal promoter region of all known sporozoite-specific genes. Promoter assays demonstrated that these sequences act as cis-acting elements and are critical for the expression of sporozoite-specific genes with different expression profiles. In transgenic parasites that express endogenous AP2-O (APETALA2 in ookinetes), but whose AP2 domain had been swapped with that of AP2-Sp, several target genes of AP2-Sp were induced in the ookinete stage. These results indicate that AP2-Sp is a major transcription factor that regulates gene expression in the sporozoite stage.