Mutant/mutation
The mutant lacks expression of CDPK3 (calcium-dependent protein kinase 3) and cyclic nucleotide phosphodiesterase, putative (PDEδ, phosphodiesterase delta; cyclic nucleotide phosphodiesterase, putative). The cdpk3 pdeδ double KO mutant was produced by crossing (in the mosquitoe) the cdpk3 KO mutant  (RMgm-154) with the pdeδ KO mutant (RMgm-308).

Protein (function)
CDPK3 belongs to an expanded family of Ca²⁺ dependent protein kinases (CDPKs). CDPKs combine an amino-terminal serine/threonine kinase domain and a carboxy-terminal calmodulin-like domain, composed of four EF hands, in the same molecule. In plants, CDPKs translate Ca²⁺ signals generated by external stimuli into cellular responses, thereby regulating cell division and differentiation, the development of tolerance to stress stimuli and the specific defense responses to pathogens.

Analyses of mutants lacking expression of CDPK3 (RMgm-154, RMgm-165, RMgm-168) indicates a role for CDPK3 in regulating productive gliding motility of ookinetes.

The following different genes encoding proteins with homology to cyclic nucleotide phosphodiesterase have been identified in Plasmodium

Analyses of a mutant lacking expression of PDEδ (RMgm-308) indicate that PDEδ has a crucial role in ookinete development and motility.

Phenotype
See also the phenotype descriptions of mutants lacking expression of PDEδ (RMgm-308) or CDPK3 (RMgm-154).
Mature ookinetes showed the aberrant morphology as described for ookinetes lacking expression of only PDEδ. However, the gliding motility of immature ookinetes (12-15h) was not affected as has been found in ookinetes lacking expression of only CDPK3. The suppressed CDPK3 ko phenotype in the cdpk3 pdeδ double KO mutant suggests an interaction between cGMP and calcium dependent signalling pathways that regulate ookinete gliding (see also 'Additional information').

Additional information
In the paper evidence is presented that in ookinetes GCß is the main source for cGMP and that a cyclic GMP signalling module exists that regulates gliding motility of ookinetes. This evidence is partly based on the analysis of mutants lacking expression PDEδ (RMgm-308) and GCβ (RMgm-307) and a mutant  lacking expression of both GCβ and PDEδ (RMgm-309). These analyses indicate that PDEδ is the relevant cGMP degrading enzyme. Signalling via a cGMP-dependent protein kinase (PKG; PF14_0346; PB000726.02.0) may regulate ookinete differentiation and motility.

Disruption of the P. falciparum ortholog of PBANKA_040820 has been attempted (Solyakov et al., 2011, Nat Commun, 2:565).
The gene is likely essential for asexual proliferation. After transfection with a KO vector a weak PCR signal diagnostic for integration was observed, indicating that integration does transiently occur but parasites with a disrupted locus do not persist. Cloning will be required to validate this interpretation for this gene.


Other mutants
RMgm-154: A mutant lacking expression of CDPK3
RMgm-165: An independent mutant lacking expression of CDPK3
RMgm-168: A mutant lacking expression of CDPK3 and expressing GFP under control of the hsp70 promoter. This mutant has been generated by crossing mutant RMgm-165 lacking expression of CDPK3 with mutant RMgm-166 that expresses GFP.
RMgm-308: A mutant lacking expression of PDEδ
RMgm-12: A mutant lacking expression CDPK4