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

Kwecka, D., Wang, Z., Eigminas, E., Liu, L., Regan, J.C., Kim, C., and Philip, N. 

By Dipika Mishra, Akiyoshi Lab

Malaria, caused by Plasmodium parasites, is a global public health burden affecting myriad people worldwide. The life cycle of the malaria parasite is a complex process involving two hosts; a mosquito and a vertebrate host. Further, to ensure transmission to the mosquito, the parasite relies on a motile ookinete stage whose apical structure ensures attachment and penetration of the mosquito midgut membrane. While previous studies have identified numerous proteins at the apical tip, the functional role of signalling proteins localised to the apical complex remain poorly understood. 

Researchers in the Philip lab have discovered the role of a cryptic cyclic nucleotide binding protein, CBP-O in establishing ookinete infection. Their findings demonstrate that CBP-O localizes to the apex of ookinetes and is critical for invasion of the mosquito midgut epithelium. Furthermore, domain analysis revealed that both N- and C-terminus of the CBP-O protein play distinct and essential functions. While the N-terminus is necessary for positioning CBP-O to the ookinete apex, the C-terminus binds to cyclic nucleotides.  CBP-O is also conserved across the phylum Apicomplexa highlighting the crucial roles of cyclic nucleotide signalling in controlling host/vector invasion by these parasites. 

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