Endoplasmic reticulum PI(3)P lipid binding targets malaria proteins to the host cell

dc.contributor.authorBhattacharjee, Souvik
dc.contributor.authorStahelin, Robert V.
dc.contributor.authorSpeicher, Kaye D.
dc.contributor.authorSpeicher, David W.
dc.contributor.authorHaldar, Kasturi
dc.contributor.departmentBiochemistry and Molecular Biology, School of Medicine
dc.date.accessioned2025-07-11T15:59:49Z
dc.date.available2025-07-11T15:59:49Z
dc.date.issued2012
dc.description.abstractHundreds of effector proteins of the human malaria parasite Plasmodium falciparum constitute a "secretome" carrying a host-targeting (HT) signal, which predicts their export from the intracellular pathogen into the surrounding erythrocyte. Cleavage of the HT signal by a parasite endoplasmic reticulum (ER) protease, plasmepsin V, is the proposed export mechanism. Here, we show that the HT signal facilitates export by recognition of the lipid phosphatidylinositol-3-phosphate (PI(3)P) in the ER, prior to and independent of protease action. Secretome HT signals, including those of major virulence determinants, bind PI(3)P with nanomolar affinity and amino acid specificities displayed by HT-mediated export. PI(3)P-enriched regions are detected within the parasite's ER and colocalize with endogenous HT signal on ER precursors, which also display high-affinity binding to PI(3)P. A related pathogenic oomycete's HT signal export is dependent on PI(3)P binding, without cleavage by plasmepsin V. Thus, PI(3)P in the ER functions in mechanisms of secretion and pathogenesis.
dc.eprint.versionAuthor's manuscript
dc.identifier.citationBhattacharjee S, Stahelin RV, Speicher KD, Speicher DW, Haldar K. Endoplasmic reticulum PI(3)P lipid binding targets malaria proteins to the host cell. Cell. 2012;148(1-2):201-212. doi:10.1016/j.cell.2011.10.051
dc.identifier.urihttps://hdl.handle.net/1805/49365
dc.language.isoen_US
dc.publisherElsevier
dc.relation.isversionof10.1016/j.cell.2011.10.051
dc.relation.journalCell
dc.rightsPublisher Policy
dc.sourcePMC
dc.subjectPlasmodium falciparum
dc.subjectPathogenic protein export
dc.subjectSecretory PI(3)P regions
dc.titleEndoplasmic reticulum PI(3)P lipid binding targets malaria proteins to the host cell
dc.typeArticle
Files
Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
Bhattacharjee2012Endoplasmic-AAM.pdf
Size:
2.91 MB
Format:
Adobe Portable Document Format
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
2.04 KB
Format:
Item-specific license agreed upon to submission
Description: