A divergent cyclic nucleotide binding protein promotes Plasmodium ookinete infection of the mosquito

Colonisation of mosquitos by the malarial parasite is critically reliant on the invasive ookinete stage. Ookinete invasion of mosquito is coordinated by the apical complex, a specialised parasite structure containing components for secretion, attachment and penetration. While studies have investigated cytoskeletal and secretory elements, it is currently unknown if signalling modules are present or functional at the apical complex. Here we elucidate the role of a cryptic cyclic nucleotide-binding protein which we name CBP-O. PbCBP-O showed a marked localisation to the ookinete apex and disruption of the protein severely compromised ookinete invasion of mosquitos. Domain dissection analysis revealed that the N- and C-termini have distinct functions. Intriguingly, PbCBP-O exhibits dual binding specificity to both cGMP and cAMP. Our findings suggest the apical tip of the ookinete is a platform to transduce cyclic nucleotide signals essential for malaria parasite transmission.