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. Attached Files Name Description MIMEType Size Downloads koningward-plasmodiumtranslocon-2020.pdf Published version application/pdf 2.09MB 15 Title Plasmodium translocon component EXP2 facilitates hepatocyte invasion Author(s) Mello-Vieira, J Enguita, FJ 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 Persistent URL http://hdl.handle.net/10536/DRO/DU:30145353 Document type: Journal Article Collections: Faculty of Health School of Medicine Open Access Collection Related Links Link Description Link to full-text (open access)     Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved. 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. Versions Version Filter Type Mon, 16 Nov 2020, 07:06:24 EST Tue, 17 Nov 2020, 04:00:43 EST Tue, 17 Nov 2020, 06:48:36 EST Sat, 28 Nov 2020, 01:43:56 EST Sat, 09 Jan 2021, 01:37:10 EST Tue, 12 Jan 2021, 05:21:15 EST Tue, 09 Feb 2021, 10:44:30 EST Tue, 09 Feb 2021, 10:45:45 EST Tue, 09 Feb 2021, 11:01:35 EST Filtered Full Citation counts:   Cited 0 times in TR Web of Science Cited 0 times in Scopus Search Google Scholar Access Statistics: 22 Abstract Views, 15 File Downloads  -  Detailed Statistics Created: Mon, 16 Nov 2020, 07:06:24 EST

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.