Mutant/mutation
The mutant lacks expression of guanylyl cyclase β (GCß).

Protein (function)
Two different genes with high homology to guanylyl cyclases (GCα and GCβ) have been identified in Plasmodium (guanylyl cyclase alpha: PF11_0395; PB001219.00.0, PB000256.00.0).
Guanylyl cyclase β (GCß) contains a guanylate cyclase domain and an N-terminal P-type ATPase like domain.

Phenotype
The phenotype analyses indicate that the GCß has a crucial role in ookinete motility, resulting in failure of invasion of the midgut epithelium and the formation of oocysts. This phenotype is similar to the phenotype of an independent mutant lacking expression of GCß (RMgm-169). See further '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 a mutant lacking expression of a cyclic nucleotide degrading phosphodiesterase (PDEδ; RMgm-308) 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.

Injection of the mutant ookinetes into the hemocoel of mosquitoes did not result in formation of salivary gland sporozoites, suggesting that GCß may have an additional function.

In the same paper it is reported that repeated attempts were made to disrupt the guanylyl cyclase-α gene (GCα; Guanylyl cyclase alpha: PB001219.00.0, PB000256.00.0; PF11_0395). These attempts were unsuccessful (see RMgm-324), suggesting its essential role in the blood stage parasites (no information is provided on the construct used to disrupt GCα and the sequence of primers used to amplify the target regions).

An independent unsuccessful attempt to disrupt the guanylyl cyclase-α gene is described in RMgm-323.

(Gene models for GCß PB000752.03.0; PB300849.03.0; PB001059)

Other mutants
RMgm-169: An independent mutant lacking expression of GCβ
RMgm-309: A mutant lacking expression of both GCβ and PDEδ (PB000873.01.0; PF14_0672; cyclic nucleotide phosphodiesterase, putative).
RMgm-323 and RMgm-324; Unsuccessful attempts to disrupt GCα; Guanylyl cyclase alpha: PB001219.00.0, PB000256.00.0; PF11_0395