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Plasmodium translocon component EXP2 facilitates hepatocyte invasion

Mello-Vieira, J, Enguita, FJ, De Koning-Ward, T, Zuzarte-Luís, V and Mota, MM 2020, Plasmodium translocon component EXP2 facilitates hepatocyte invasion, Nature Communications, vol. 11, no. 1, pp. 1-13, doi: 10.1038/s41467-020-19492-4.

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Title Plasmodium translocon component EXP2 facilitates hepatocyte invasion
Author(s) Mello-Vieira, J
Enguita, FJ
De Koning-Ward, TORCID iD for De Koning-Ward, T orcid.org/0000-0001-5810-8063
Zuzarte-Luís, V
Mota, MM
Journal name Nature Communications
Volume number 11
Issue number 1
Article ID 5654
Start page 1
End page 13
Total pages 13
Publisher Nature Research
Place of publication Berlin, Germany
Publication date 2020-11-06
ISSN 2041-1723
2041-1723
Keyword(s) Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
HOST-CELL INVASION
KINASE-C-ZETA
MALARIA PARASITE
TRYPANOSOMA-CRUZI
MAMMALIAN-CELLS
MEMBRANE DAMAGE
PROTEIN EXPORT
FALCIPARUM
SPHINGOMYELINASE
SPOROZOITES
Summary Plasmodium parasites possess a translocon that exports parasite proteins into the infected erythrocyte. Although the translocon components are also expressed during the mosquito and liver stage of infection, their function remains unexplored. Here, using a combination of genetic and chemical assays, we show that the translocon component Exported Protein 2 (EXP2) is critical for invasion of hepatocytes. EXP2 is a pore-forming protein that is secreted from the sporozoite upon contact with the host cell milieu. EXP2-deficient sporozoites are impaired in invasion, which can be rescued by the exogenous administration of recombinant EXP2 and alpha-hemolysin (an S. aureus pore-forming protein), as well as by acid sphingomyelinase. The latter, together with the negative impact of chemical and genetic inhibition of acid sphingomyelinase on invasion, reveals that EXP2 pore-forming activity induces hepatocyte membrane repair, which plays a key role in parasite invasion. Overall, our findings establish a novel and critical function for EXP2 that leads to an active participation of the host cell in Plasmodium sporozoite invasion, challenging the current view of the establishment of liver stage infection.
Language eng
DOI 10.1038/s41467-020-19492-4
Indigenous content off
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2020, The Author(s)
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30145353

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
Open Access Collection
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.