Abstract
In malaria parasites, male gametogenesis is a proliferative stage essential for parasite transmission to the mosquito vector. It is a rapid process involving three rounds of genome replication alternating with closed endomitoses, and assembly of axonemes to produce eight flagellated motile microgametes. Studies in Plasmodium berghei have highlighted tight regulation of gametogenesis by a network of kinases. The P. berghei MAPK homologue PbMAP-2 is dispensable for asexual development but important at the induction of axoneme motility. However, in P. falciparum, causing the most severe form of human malaria, PfMAP-2 was suggested to be essential for asexual proliferation indicating distinct functions for MAP-2 in these two Plasmodium species. We here show that PfMAP-2 is dispensable for asexual growth but important for male gametogenesis in vitro. Similar to PbMAP-2, PfMAP-2 is required for initiating axonemal beating but not for prior DNA replication or axoneme formation. In addition, single and double null mutants of PfMAP-2 and the second P. falciparum MAPK homologue PfMAP-1 show no defect in asexual proliferation, sexual commitment or gametocytogenesis. Our results suggest that MAPK activity plays no major role in the biology of both asexual and sexual blood stage parasites up until the point of male gametogenesis.
Highlights
In malaria parasites, male gametogenesis is a proliferative stage essential for parasite transmission to the mosquito vector
We demonstrate that similar to the situation in P. berghei, PfMAP-1 and PfMAP-2 are dispensable for asexual proliferation, sexual commitment and gametocyte development and that PfMAP-2 shows male-specific expression and is essential for male gametogenesis
Our experiments revealed that compared to wild type (WT) gametocytes (100% ± 37.6), parasites devoid of the PfMAP-2 kinase displayed a dramatic decrease in the relative number of exflagellation centres formed (4.9% ± 3.3) (p = 0.0002; unpaired two-tailed Student’s t test) (Fig. 2c)
Summary
Male gametogenesis is a proliferative stage essential for parasite transmission to the mosquito vector It is a rapid process involving three rounds of genome replication alternating with closed endomitoses, and assembly of axonemes to produce eight flagellated motile microgametes. Our results suggest that MAPK activity plays no major role in the biology of both asexual and sexual blood stage parasites up until the point of male gametogenesis. Gametogenesis is linked to intracellular mobilisation of Ca2+, which in male gametocytes activates three rounds of rapid replication of DNA followed by endomitosis[16] During this process, parasites egress from the RBC and start axoneme biosynthesis. Following Ca2+ mobilisation, the action of the calcium-dependent protein kinase 4 (CDPK4) is essential for microgamete development at three different steps including the initiation of axoneme m otility[18,22,23]. Due to these defects PbMAP-2 KO parasites were essentially unable to infect Anopheles mosquitoes[28,29]
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