Malaria Transmission Assisted by Interaction Between Plasmodium Α-Tubulin-i and Anopheles FREP1 Protein

Invasion of the mosquito midgut by Plasmodium parasites is essential for malaria transmission. FREP1, a mosquito midgut peritrophic matrix protein, binds to the parasite ookinete stage and mediates Plasmodium infection of Anopheles mosquitoes. The FREP1-mediated Plasmodium invasion pathway is highly conserved across multiple species of Plasmodium and Anopheles. During mosquito infection, ookinetes must orient their apical invasion apparatus toward the midgut epithelium. Here, we conducted biochemical and cell biological studies to identify Plasmodium ookinete proteins that bind mosquito FREP1. Among these newly identified FREP1-binding partners (FBP), we demonstrate that Plasmodium α-tubulin-I at the ookinete apical complex is critical for invasion. Cell biological studies revealed that anti-α-tubulin antibodies bound to the apical polar ring of the living P. falciparum ookinetes. Functional analyses showed that polyclonal serum directed against P. falciparum α-tubulin-I, but not other FBPs, significantly reduced the number of P. falciparum oocysts in An. gambiae midguts. Our data support that interactions between Anopheles FREP1 protein and Plasmodium α-tubulin-I anchors and directs the ookinete invasive apparatus towards midgut peritrophic matrix, which is critical for the efficient invasion and transmission of Plasmodium to mosquitoes. Thus, Anopheles FREP1 and Plasmodium α-tubulin-I are potential targets for blocking malaria transmission.