RRC ID 65040
Author Romano JD, Sonda S, Bergbower E, Smith ME, Coppens I.
Title Toxoplasma gondii salvages sphingolipids from the host Golgi through the rerouting of selected Rab vesicles to the parasitophorous vacuole.
Journal Mol Biol Cell
Abstract The obligate intracellular protozoan Toxoplasma gondii actively invades mammalian cells and, upon entry, forms its own membrane-bound compartment, named the parasitophorous vacuole (PV). Within the PV, the parasite replicates and scavenges nutrients, including lipids, from host organelles. Although T. gondii can synthesize sphingolipids de novo, it also scavenges these lipids from the host Golgi. How the parasite obtains sphingolipids from the Golgi remains unclear, as the PV avoids fusion with host organelles. In this study, we explore the host Golgi-PV interaction and evaluate the importance of host-derived sphingolipids for parasite growth. We demonstrate that the PV preferentially localizes near the host Golgi early during infection and remains closely associated with this organelle throughout infection. The parasite subverts the structure of the host Golgi, resulting in its fragmentation into numerous ministacks, which surround the PV, and hijacks host Golgi-derived vesicles within the PV. These vesicles, marked with Rab14, Rab30, or Rab43, colocalize with host-derived sphingolipids in the vacuolar space. Scavenged sphingolipids contribute to parasite replication since alterations in host sphingolipid metabolism are detrimental for the parasite's growth. Thus our results reveal that T. gondii relies on host-derived sphingolipids for its development and scavenges these lipids via Golgi-derived vesicles.
Volume 24(12)
Pages 1974-95
Published 2013-6-1
DOI 10.1091/mbc.E12-11-0827
PII mbc.E12-11-0827
PMID 23615442
PMC PMC3681701
MeSH Animals CHO Cells Cell Line Chlorocebus aethiops Cricetinae Cricetulus Cytoplasmic Vesicles / metabolism* Cytoplasmic Vesicles / parasitology Cytoplasmic Vesicles / ultrastructure Golgi Apparatus / metabolism* Golgi Apparatus / parasitology Golgi Apparatus / ultrastructure Green Fluorescent Proteins / genetics Green Fluorescent Proteins / metabolism HeLa Cells Host-Parasite Interactions Humans Immunoblotting Microscopy, Electron, Transmission Microscopy, Fluorescence Mutation Sphingolipids / metabolism* Toxoplasma / growth & development Toxoplasma / metabolism* Toxoplasma / physiology Vacuoles / metabolism* Vacuoles / parasitology Vacuoles / ultrastructure Vero Cells rab GTP-Binding Proteins / genetics rab GTP-Binding Proteins / metabolism*
IF 3.791
Human and Animal Cells LY-B(RCB1698)