Peculiarities of host cholesterol transport to the unique intracellular vacuole containing Toxoplasma

Alfica Sehgal, Silvana Bettiol, Marc Pypaert, Markus R. Wenk, Achim Kaasch, Ira J. Blader, Keith A. Joiner, Isabelle Coppens

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

The intracellular protozoan Toxoplasma gondii is auxo-trophic for low-density lipoprotein (LDL)-derived cholesterol (C). We previously showed that T. gondii scavenges this essential lipid from host endolysosomal compartments and that C delivery to the parasitophorous vacuole (PV) does not require transit through host Golgi or encdoplasmic reticulum. In this study, we explore the itinerary of C from the host endolysosomes; to the PV. Labeled C incorporated into LDL is rapidly detected in intravacuolar parasites and partially esterified by the parasites. In contrast to diverse mammalian organelles, the post-endolysosomal transfer of to the PV does not involve the host plasma membrane as an intermediate. Nevertheless, the PV membrane is accessible to extracellular sterol acceptors, suggesting C trafficking from intracellular parasites to host plasma membrane. C movement to the PV requires temperatures permissive for vesicular transport, metabolic energy and functional microtubules Host caveolae vesicles and the sterol carrier protein-2 do not participate in this process. Proteolytic treatment of purified PV or free parasites abolishes C acquisition by the parasites. Altogether, these results support a vesicular transport system from host endolysosomes to the PV, and a requirement for PV membrane and parasite plasma membrane proteins in C delivery to T. gondii.

Original languageEnglish (US)
Pages (from-to)1125-1141
Number of pages17
JournalTraffic
Volume6
Issue number12
DOIs
StatePublished - Dec 2005

Keywords

  • Apicomplexa
  • Cholesterol efflux
  • Intracellular cholesterol trafficking
  • Intravacuolar parasitism
  • LDL-derived cholesterol
  • Microtubules

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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