Mutant/mutation
The mutant lacks expression of eukaryotic initiation factor- 2α (eIF2α) kinase (IK2)

Protein (function)
One control mechanism of protein synthesis in eukaryotic cells involves the phosphorylation of the α-subunit of eukaryotic translation-initiation factor-2 (eIF-2α). During initiation of protein synthesis, a ternary complex of Met-tRNA, GTP, and the eukaryotic initiation factor 2 (eIF2) is delivered to the translation initiation machinery. During this translation process, eIF2-GTP is hydrolyzed to eIF2-GDP and released from the machinery. A guanine nucleotide exchange factor (eIF2B) facilitates the exchange of eIF2-GDP to eIF2-GTP, which is a requisite for a new round of translation. The phosphorylation of eIF2α blocks the recycling of eIF2-GTP and downregulates protein synthesis. The phosphorylation of eIF2α is associated with the appearance of stress granules in the cytoplasm of stressed cells.

Three eIF2α kinases, IK1 (PF14_0423; eukaryotic initiation factor 2alpha kinase 1), IK2 (PfA0380w; PBANKA_020580; serine/threonine protein kinase, putative), and PK4 (PFF1370w; PBANKA_112690; protein kinase PK4), have been identified in Plasmodium (Fenell C et al. 2009. Malar J. 8, 99).

Phenotype
Phenotype analyses indicate that IK2 is not essential for blood stage development and the formation of oocysts and salivary gland sporozoites. Sporozoites show however a strongly reduced infectivity.
Evidence is presented that in the absence of IK2, eIF2α is not phosphorylated in the mutant sporozoites and protein synthesis is enhanced.
Evidence is presented that IK2 activity leads to inhibition of translation in salivary gland sporozoites and accumulation of 'stalled' mRNAs into granules
Evidence is presented that mutant salivary gland sporozoites prematurely develop into liver stages, indicating that sporozoite 'latency' (arrested development in salivary glands) is controlled by IK2.

See RMgm-532 for an  independent P. berghei mutant lacking expression of IK2 (PBANKA_020580). Phenotype analyses of this mutant showed the following characteristics: Ookinete numbers (in vitro) reduced to 52% of wild type; Oocyst numbers (day 12-14) reduced to 20% of wild type; Sporozoites NOT different from wild type; Transmitted by mosquito bite.

See below for a picture showing the location of the target regions used to disrupt PBANKA_020580 in the mutant described here and for mutant RMgm-532

Additional information
The phenotype is based on the analysis of mutants obtained from a single transfection experiment.

In this study also the P. falciparum orthologous gene PfeIK2 (PfA0380w) was disrupted by single-crossover homologous recombination. Clones of PfeIK2(-) completed the sexual development in mosquitoes and sporozoites invaded the salivary glands in numbers similar to wild-type.

Evidence is presented that in wild type parasites 'stalled' mRNAs accumulate in RNA granules whereas in the absence of IK2, RNA granules and and levels of bulk poly(A) RNA were strongly decreased in the mutant sporozoites.

The analysis of the morphology of mutant sporozoites by light- and transmission electron microscopy provided evidence for premature development of salivary gland sporozoites into liver stages (as shown by the formation of 'bulbs' and IMC (inner membrane complex) disruption in sporozoites.

See RMgm-483 for negative attempts to disrupt protein kinase PK4 (PFF1370w; PBANKA_112690) in P. berghei , indicating an essential role of PK4 during asexual blood stage development.

Evidence has been presented that P. falciparum IK1 (PF14_0423; eukaryotic initiation factor 2alpha kinase 1) is not required for P. falciparum asexual and sexual blood stage development and sporozoite formation (Fenell C et al. 2009. Malar J. 8, 99). Evidence is provided that PfeIK1, is able to phosphorylate the P. falciparum eIF2α orthologue (PF07_0117) in vitro and that eIF2α phosphorylation in response to starvation is abolished in asexual parasites lacking expression of IK1.

Disruption of the P. falciparum ortholog has been attempted (Solyakov et al., 2011, Nat Commun, 2:565). After transfection with a KO vector a strong PCR signal diagnostic for gene disruption was observed in transfected populations indicating that this gene is not essential for asexual proliferation. Cloning will however be required to validate this interpretation for this

Other mutants
RMgm-483 - negative attempts to disrupt protein kinase PK4 (PFF1370w; PBANKA_112690) in P. berghei
RMgm-532 - An  independent P. berghei mutant lacking expression of IK2 (PBANKA_020580)