BIROn - Birkbeck Institutional Research Online

    Formation of ER-lumenal intermediates during export of Plasmodium proteins containing transmembrane-like hydrophobic sequences

    Levray, Y.S. and Bana, Bianca and Tarr, S.J. and McLaughlin, E.J. and Rossi-Smith, P. and Waltho, A. and Charlton, G.H. and Zenezini Chiozzi, R. and Straton, C.R. and Thalassinos, Kostas and Osborne, Andrew (2023) Formation of ER-lumenal intermediates during export of Plasmodium proteins containing transmembrane-like hydrophobic sequences. PLoS Pathogens , ISSN 1553-7374.

    [img] Text
    Levray%20RPS-combined.pdf - Author's Accepted Manuscript
    Restricted to Repository staff only

    Download (22MB)
    [img]
    Preview
    Text
    51162a.pdf - Published Version of Record
    Available under License Creative Commons Attribution.

    Download (3MB) | Preview
    Link to Research Data: https://www.ebi.ac.uk/pride/

    Abstract

    During the blood stage of a malaria infection, malaria parasites export both soluble and membrane proteins into the erythrocytes in which they reside. Exported proteins are trafficked via the parasite endoplasmic reticulum and secretory pathway, before being exported across the parasitophorous vacuole membrane into the erythrocyte. Transport across the parasitophorous vacuole membrane requires protein unfolding, and in the case of membrane proteins, extraction from the parasite plasma membrane. We show that trafficking of the exported Plasmodium protein, Pf332, differs from that of canonical eukaryotic soluble-secreted and transmembrane proteins. Pf332 is initially ER-targeted by an internal hydrophobic sequence that unlike a signal peptide, is not proteolytically removed, and unlike a transmembrane segment, does not span the ER membrane. Rather, both termini of the hydrophobic sequence enter the ER lumen and the ER-lumenal species is a productive intermediate for protein export. Furthermore, we show in intact cells, that two other exported membrane proteins, SBP1 and MAHRP2, assume a lumenal topology within the parasite secretory pathway. Although the addition of a C-terminal ER-retention sequence, recognised by the lumenal domain of the KDEL receptor, does not completely block export of SBP1 and MAHRP2, it does enhance their retention in the parasite ER. This indicates that a sub-population of each protein adopts an ER-lumenal state that is an intermediate in the export process. Overall, this suggests that although many exported proteins traverse the parasite secretory pathway as typical soluble or membrane proteins, some exported proteins that are ER-targeted by a transmembrane segment-like, internal, non-cleaved hydrophobic segment, do not integrate into the ER membrane, and form an ER-lumenal species that is a productive export intermediate. This represents a novel means, not seen in typical membrane proteins found in model systems, by which exported transmembrane-like proteins can be targeted and trafficked within the lumen of the secretory pathway.

    Metadata

    Item Type: Article
    School: Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences
    Depositing User: Andrew Osborne
    Date Deposited: 05 May 2023 12:59
    Last Modified: 02 Aug 2023 18:21
    URI: https://eprints.bbk.ac.uk/id/eprint/51162

    Statistics

    Activity Overview
    6 month trend
    16Downloads
    6 month trend
    72Hits

    Additional statistics are available via IRStats2.

    Archive Staff Only (login required)

    Edit/View Item Edit/View Item