Mutant/mutation
The mutant lacks expression of  adenylyl cyclase 1(ACα)

Protein (function)
Two different genes with high homology to ACs (ACα and ACβ) have been identified in Plasmodium ( adenylyl cyclase beta: MAL8P1.150; PB000487.01.0) In particular, ACα was shown to have AC activity in P. falciparum. Acα genes from Plasmodium, Paramecium and Tetrahimena are closely related and their sequence includes a domain with high homology to K+ channels. In Paramecium, where the purified AC protein also has K+ channel activity, generation of cAMP is regulated by K+ conductance. It is thought that ACα presents a transmembrane K+-channel domain and an intracellular AC domain, which are functionally linked (Baker et al., 2004, IUBMB Life 56, 535-540).

Phenotype
In other studies evidence has been presented that suggest that migration through cells induces apical exocytosis in Plasmodium sporozoites, resulting in the exposure of adhesive domains of proteins (TRAP, SSP2) in the apical end of sporozoites, a process that may facilitate invasion of hepatocytes. Biochemical analyses indicate that regulated exocytosis was not activated in mutant sporozoites. Mutant sporozoites lacking expression of adenylyl cyclase, the enzyme that synthesizes cAMP, are not able to expose the adhesive proteins and their infectivity is reduced by half.

Additional information
Two P. falciparum gene models (PF14_0778, PF14_0043) and two P. berghei gene models (PB001333.02.0; PB106447.00.0) exist.

Biochemical analyses indicate that increases in cAMP levels in sporozoites mediate apical regulated exocytosis, which activates sporozoites for host cell invasion. By analysis of the mutant deficient in adenylyl cyclase α (ACα), evidence is presented that suggest that the cAMP signaling pathway is essential to induce apical exocytosis, which is activated during migration through cells.

To confirm that the phenotype observed in the mutant PbACα- sporozoites is caused specifically by depletion of the Pbacα gene, one of the PbACα- lines was complemented with ACα using a DNA construct with the human (h) dhfr selectable marker and two fragments of 4.3kb (5′) and 0.5 kb (3′) of the ACα gene of P. berghei. The linearized vector  integrates into the  acα locus. Selection of transformed parasites was performed by treating infected animals with WR99210 (20 mg/kg bodyweight)]. One parasite clone (Cmp) in which the acα gene was integrated into the acα locus was selected for analysis.

Other mutants