ISP1-Anchored Polarization of GCβ/CDC50A Complex Initiates Malaria Ookinete Gliding Motility

• DOI: 10.1016/j.cub.2018.06.069
• Publication Date: 2018-08-23T10:41:59Z
• Authors: Han Gao; Zhenke Yang; Xu Wang; Pengge Qian; Renjie Hong; Xin Chen; Xin-zhuan Su; Huiting Cui; Jing Yuan
• Keywords: Gliding motility; Cyclic guanosine monophosphate; Cyclic adenosine monophosphate

Ookinete gliding motility is essential for penetration of the mosquito midgut wall and transmission malaria parasites. Cyclic guanosine monophosphate (cGMP) signaling has been implicated in ookinete gliding. However, upstream mechanism how parasites activate cGMP thus initiate remains unknown. Using real-time imaging to visualize Plasmodium yoelii guanylate cyclase β (GCβ), we show that cytoplasmic GCβ translocates polarizes parasite plasma membrane at "ookinete extrados site" (OES) during zygote-to-ookinete differentiation. The polarization enzymatic active OES initiates matured ookinete. Both P4-ATPase-like domain are required CDC50A, a co-factor P4-ATPase, binds stabilizes development. Screening inner complex proteins identifies ISP1 as key molecule anchors GCβ/CDC50A mature ookinetes. This study defines spatial-temporal initiation gliding, where likely elevates local levels activates cGMP-dependent protein kinase signaling.