Malaria parasites utilize two essential plasma membrane fusogens for gamete fertilization

Sudhir Kumar; Clari Valansi; Meseret T. Haile; Xiaohui Li; Kateryna Flyak; Abhisek Dwivedy; Biley A. Abatiyow; Amanda S. Leeb; Spencer Y. Kennedy; Nelly M. Camargo; Ashley M. Vaughan; Nicolas G. Brukman; Benjamin Podbilewicz; Stefan H.I. Kappe

doi:10.1007/s00018-022-04583-w

Malaria parasites utilize two essential plasma membrane fusogens for gamete fertilization

Sudhir Kumar, Clari Valansi, Meseret T. Haile, Xiaohui Li, Kateryna Flyak, Abhisek Dwivedy, Biley A. Abatiyow, Amanda S. Leeb, Spencer Y. Kennedy, Nelly M. Camargo, Ashley M. Vaughan, Nicolas G. Brukman, Benjamin Podbilewicz, Stefan H.I. Kappe

Biology

Technion - Israel Institute of Technology

Research output: Contribution to journal › Article › peer-review

Abstract

Cell fusion of female and male gametes is the climax of sexual reproduction. In many organisms, the Hapless 2 (HAP2) family of proteins play a critical role in gamete fusion. We find that Plasmodium falciparum, the causative agent of human malaria, expresses two HAP2 proteins: PfHAP2 and PfHAP2p. These proteins are present in stage V gametocytes and localize throughout the flagellum of male gametes. Gene deletion analysis and genetic crosses show that PfHAP2 and PfHAP2p individually are essential for male fertility and thereby, parasite transmission to the mosquito. Using a cell fusion assay, we demonstrate that PfHAP2 and PfHAP2p are both authentic plasma membrane fusogens. Our results establish nonredundant essential roles for PfHAP2 and PfHAP2p in mediating gamete fusion in Plasmodium and suggest avenues in the design of novel strategies to prevent malaria parasite transmission from humans to mosquitoes.

Original language	English
Article number	549
Journal	Cellular and Molecular Life Sciences
Volume	79
Issue number	11
DOIs	https://doi.org/10.1007/s00018-022-04583-w
State	Published - Nov 2022

Keywords

Cell fusion
Gametocyte
Macrogamete
Microgamete
Plasmodium
Transmission

All Science Journal Classification (ASJC) codes

Molecular Medicine
Molecular Biology
Pharmacology
Cellular and Molecular Neuroscience
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s00018-022-04583-w

Cite this

Kumar, S., Valansi, C., Haile, M. T., Li, X., Flyak, K., Dwivedy, A., Abatiyow, B. A., Leeb, A. S., Kennedy, S. Y., Camargo, N. M., Vaughan, A. M., Brukman, N. G., Podbilewicz, B., & Kappe, S. H. I. (2022). Malaria parasites utilize two essential plasma membrane fusogens for gamete fertilization. Cellular and Molecular Life Sciences, 79(11), Article 549. https://doi.org/10.1007/s00018-022-04583-w

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title = "Malaria parasites utilize two essential plasma membrane fusogens for gamete fertilization",

abstract = "Cell fusion of female and male gametes is the climax of sexual reproduction. In many organisms, the Hapless 2 (HAP2) family of proteins play a critical role in gamete fusion. We find that Plasmodium falciparum, the causative agent of human malaria, expresses two HAP2 proteins: PfHAP2 and PfHAP2p. These proteins are present in stage V gametocytes and localize throughout the flagellum of male gametes. Gene deletion analysis and genetic crosses show that PfHAP2 and PfHAP2p individually are essential for male fertility and thereby, parasite transmission to the mosquito. Using a cell fusion assay, we demonstrate that PfHAP2 and PfHAP2p are both authentic plasma membrane fusogens. Our results establish nonredundant essential roles for PfHAP2 and PfHAP2p in mediating gamete fusion in Plasmodium and suggest avenues in the design of novel strategies to prevent malaria parasite transmission from humans to mosquitoes.",

keywords = "Cell fusion, Gametocyte, Macrogamete, Microgamete, Plasmodium, Transmission",

author = "Sudhir Kumar and Clari Valansi and Haile, {Meseret T.} and Xiaohui Li and Kateryna Flyak and Abhisek Dwivedy and Abatiyow, {Biley A.} and Leeb, {Amanda S.} and Kennedy, {Spencer Y.} and Camargo, {Nelly M.} and Vaughan, {Ashley M.} and Brukman, {Nicolas G.} and Benjamin Podbilewicz and Kappe, {Stefan H.I.}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature Switzerland AG.",

year = "2022",

month = nov,

doi = "10.1007/s00018-022-04583-w",

language = "الإنجليزيّة",

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TY - JOUR

T1 - Malaria parasites utilize two essential plasma membrane fusogens for gamete fertilization

AU - Kumar, Sudhir

AU - Valansi, Clari

AU - Haile, Meseret T.

AU - Li, Xiaohui

AU - Flyak, Kateryna

AU - Dwivedy, Abhisek

AU - Abatiyow, Biley A.

AU - Leeb, Amanda S.

AU - Kennedy, Spencer Y.

AU - Camargo, Nelly M.

AU - Vaughan, Ashley M.

AU - Brukman, Nicolas G.

AU - Podbilewicz, Benjamin

AU - Kappe, Stefan H.I.

PY - 2022/11

Y1 - 2022/11

N2 - Cell fusion of female and male gametes is the climax of sexual reproduction. In many organisms, the Hapless 2 (HAP2) family of proteins play a critical role in gamete fusion. We find that Plasmodium falciparum, the causative agent of human malaria, expresses two HAP2 proteins: PfHAP2 and PfHAP2p. These proteins are present in stage V gametocytes and localize throughout the flagellum of male gametes. Gene deletion analysis and genetic crosses show that PfHAP2 and PfHAP2p individually are essential for male fertility and thereby, parasite transmission to the mosquito. Using a cell fusion assay, we demonstrate that PfHAP2 and PfHAP2p are both authentic plasma membrane fusogens. Our results establish nonredundant essential roles for PfHAP2 and PfHAP2p in mediating gamete fusion in Plasmodium and suggest avenues in the design of novel strategies to prevent malaria parasite transmission from humans to mosquitoes.

AB - Cell fusion of female and male gametes is the climax of sexual reproduction. In many organisms, the Hapless 2 (HAP2) family of proteins play a critical role in gamete fusion. We find that Plasmodium falciparum, the causative agent of human malaria, expresses two HAP2 proteins: PfHAP2 and PfHAP2p. These proteins are present in stage V gametocytes and localize throughout the flagellum of male gametes. Gene deletion analysis and genetic crosses show that PfHAP2 and PfHAP2p individually are essential for male fertility and thereby, parasite transmission to the mosquito. Using a cell fusion assay, we demonstrate that PfHAP2 and PfHAP2p are both authentic plasma membrane fusogens. Our results establish nonredundant essential roles for PfHAP2 and PfHAP2p in mediating gamete fusion in Plasmodium and suggest avenues in the design of novel strategies to prevent malaria parasite transmission from humans to mosquitoes.

KW - Cell fusion

KW - Gametocyte

KW - Macrogamete

KW - Microgamete

KW - Plasmodium

KW - Transmission

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U2 - 10.1007/s00018-022-04583-w

DO - 10.1007/s00018-022-04583-w

M3 - مقالة

C2 - 36241929

SN - 1420-682X

VL - 79

JO - Cellular and Molecular Life Sciences

JF - Cellular and Molecular Life Sciences

IS - 11

M1 - 549

ER -

Malaria parasites utilize two essential plasma membrane fusogens for gamete fertilization

Abstract

Keywords

All Science Journal Classification (ASJC) codes

UN SDGs

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