Mutant/mutation
The mutant lacks expression of PDEγ and expresses GFP under the control of the constitutive eef1a promoter

Protein (function)
The cyclic nucleotides cAMP and cyclic GMP (cGMP) function as signaling second messengers downstream of surface receptor-ligand interactions by activating cAMP-dependent protein kinase (PKA) and cGMP-dependent protein kinase (PKG), respectively. Signaling through cAMP and cGMP is regulated by phosphodiesterases (PDEs), metal ion-dependent enzymes that hydrolyze the 3"-phosphoester bond of cAMP and cGMP. The Plasmodium genome encodes four PDEs (α, β, γ, and δ).
PDEγ is predicted to be a 782-amino-acid type II membrane protein with six transmembrane domains. A search for the presence of domains using the PDE sequence on Prosite (http://prosite.expasy.org/) predicted the protein to possess the conserved catalytic domain amino acid signature H-D-I-g-H-f-G-r-t-N-m-F for PDEs

Phenotype
Blood stages of the mutant show a slightly reduced growth rate.
Strongly reduced numbers of salivary gland sporozoites while normal numbers of oocyst-derived sporozoites are formed indicating a defect in invasion of salivary glands. Sporozoites show a strongly reduced gliding motility. Evidence is presented that pdeγ(-) sporozoites exhibit elevated cGMP levels and that transcript abundance for proteins involved in motility and invasion is downregulated in pdeγ(-) sporozoites.

Additional information
A blood stage growth assay was performed to determine whether there was a difference in the kinetics of growth between wild-type (WT) and pdeγ(-) parasites. Swiss Webster (SW) mice were injected intravenously (i.v.) with WT and pdeγ(-) clones, and parasitemia was analyzed daily by microscopic examination of Giemsa-stained thin blood smears for 20 days. Parasitemias were comparable between WT and both pdeγ(-) clones during the initial phase of BS growth (from days 1 through 9). However, WT and pdeγ(-) parasites differed in growth kinetics from days 10 through 15. The peak average parasitemia in mice infected with WT parasites was ~16%, which was ~2-fold higher than the peak average parasitemia of ~8% in mice infected with the pdeγ(-) clones. During later stages of growth (day 12 onward), the pdeγ(-) clones were cleared from mice earlier than WT parasites. These data show that PDE is not essential for BS parasite growth and replication.

Other mutants