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

Current Biology : CB
Han GaoJing Yuan

Abstract

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

Citations

Jun 27, 2019·Life Science Alliance·Özlem Günay-EsiyokNishith Gupta
Nov 9, 2019·Biological Reviews of the Cambridge Philosophical Society·Rowena E Martin
Sep 11, 2019·Annual Review of Microbiology·Hugo Bisio, Dominique Soldati-Favre
Dec 12, 2020·Molecular and Biochemical Parasitology·Chuanyuan LiuJing Yuan
Dec 19, 2020·Computational and Structural Biotechnology Journal·Kim Chi VoNishith Gupta
Jan 26, 2021·Frontiers in Cellular and Infection Microbiology·Josie Liane FerreiraTim-Wolf Gilberger
Mar 20, 2020·Trends in Parasitology·Özlem Günay-Esiyok, Nishith Gupta
Jun 4, 2020·Trends in Parasitology·Nicolas Dos Santos PachecoDominique Soldati-Favre
Aug 31, 2021·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Margarida Ressurreição, Christiaan van Ooij

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