Yuan Jing's research group revealed the key molecules for malaria parasite morphological control and transmission of Anopheles malaria

On December 20, Yuan Jing's group published an online publication entitled "Apical anchorage and stabilization of subpellicular microtubules by apical polar ring ensures Plasmodium ookinete infection in mosquito" online in the journal Nature Communications Research papers
.
This study reveals the apical polar ring anchoring kinezygote epimembrane microtubules and molecular cellular mechanisms
that regulate cell deformation.

Malaria parasites are parasitic protozoan pathogens that infect hundreds of millions of people and kill more than 600,000 people each year
.
Transmission of malaria relies heavily on female Anopheles mosquitoes
.
After a malaria patient is bitten by an Anopheles mosquito and sucks blood, the malaria parasite enters the midgut
of Anopheles mosquitoes as "food" with the blood.
To avoid being broken down by digestive enzymes, the malaria parasite has evolved highly effective adaptive mechanisms
for infection, parasitism, and transmission.
In the midgut lumen, Zygote needs to be transformed into a crescent-shaped Ookinete to cross the midgut epithelium and colonize the basal (body cavity) side of the midgut to establish Anopheles mosquito infection
.
Dynamic zygotic deformation, including polar protrusion-polar extension-maturation, relies on the establishment
of the epimembrane microtubule skeleton.

The zygote has 60 epimembrane microtubules with an axial distribution of apical-basal, emanating from the apex of the cell to the caudal end (10-15 um in length) with adjacent microtubules spaced 100 nm (Figure 1).

Epimembrane microtubules are essential cellular structures for zygotic deformation and malaria parasite transmission, but the mechanism of epimembrane microtubule skeleton establishment and maintenance is unknown
.
The authors previously revealed the function and mechanism of kinezygous intimal complex proteins ISP1 and ISP3 as anchoring molecules to achieve microtubule epimembrane anchoring (The EMBO Journal, 2020), and established a component protein identification and super-resolution imaging method for the subcellular structure of the malaria parasite (eLife, 2022).

Fig.
1.
Structure of microtubules in the surface membrane of zygote zygotes of Plasmodium parasites (super-resolution imaging)

In this study, a apical polar cyclin APR2 was identified by protein localization screening.
Genetic and biochemical analysis showed that APR2 is a microtubule-binding protein and participates in the apical anchoring of epimembrane microtubules; APR2 is missing, the morphology of the zygotic is completely blocked, and transmission of Anopheles malaria parasite mosquitoes is blocked
.
In terms of molecular mechanism, the apical polar ring proteome of kinezygotes was identified for the first time through protein proximity labeling method and protein profiling.
On this basis, combined with yeast two-hybrid screening and genetic function analysis, the functional module "APR2-APRp2-APRp4" for apical anchoring of the epimembrane microtubules of Plasmodium parasites was identified, in which the amino end of APR2 was responsible for direct binding to the microtubule, and the carboxyl end was responsible for direct binding to APRp2 and APRp4 to jointly maintain the structural integrity of the apical polar ring and the apical anchorage of the epimembrane microtubule (Figure 2).

Fig.
2 Apical polar ring regulation of apical zygote epimembrane microtubule anchorage in malaria parasites

In addition, this study uses biotin proximity labeling and super-resolution imaging to analyze the three-dimensional spatial structure of the apical polar ring of the mozygote for the first time, which provides a structural basis for subsequent in-depth study of the function of the apical polar ring (Figure 3).

Figure 3: Super-resolution structure of the apical polar ring of a movzygote

(Left: Side view, Middle: Top view, Right: 3D reconstruction)

Qian Pengge, a doctoral graduate of Xiamen University, Wang Xu, a postdoctoral fellow, and Guan Cuirong, a doctoral student of Wuhan University, are the first authors of this paper.
Professor Yuan Jing of Xiamen University and Professor Jiang Kai of Wuhan University are the corresponding authors of this paper, and Xiamen University is the first to complete
.
The research was supported
by the National Natural Science Foundation of China and the President's Fund of Xiamen University.

Link to the full text of the paper: class="vsbcontent_end" _msthash="101749" _msttexthash="1031069">(Photo: Wen Yuan Jing's research group)