PfSRPK1 regulates asexual blood stage schizogony and is essential for male gamete formation

Serine/arginine-rich protein kinases (SRPK) are cell cycle-regulated serine/threonine protein kinases and are important regulators of splicing factors. In this study, we functionally characterize SRPK1 of the human malaria parasite Plasmodium falciparum (Pf). PfSRPK1 was expressed in asexual blood stages and sexual stage gametocytes. Pfsrpk1¯ parasites formed asexual schizonts that generated far fewer merozoites when compared to wildtype parasites, causing reduced replication rates. Pfsrpk1¯parasites also showed a severe defect in the differentiation of male gametes, causing a complete block in parasite transmission to mosquitoes. RNA-seq analysis of wildtype PfNF54 and Pfsrpk1¯ stage V gametocytes suggested a role for PfSRPK1 in regulating transcript splicing and transcript abundance of genes coding for (i) microtubule/cilium morphogenesis related proteins, (ii) proteins involved in cyclic nucleotide metabolic processes, (iii) proteins involved in signaling such as PfMAP2, (iv) lipid metabolism enzymes, (v) proteins of the osmophilic bodies and (vi) crystalloid components. Our study reveals an essential role for PfSRPK1 in parasite cell morphogenesis and suggests this kinase as a target to prevent malaria transmission from man to mosquito. Stage V gametocyte samples from WT (control) and SRPK1-KO (KO) parasites were analyzed for transcriptional perturbations.