Unusual Sorting Mechanisms to Deliver Transmembrane Proteins into the Host-Cell Vacuole

Traffic. 2008 Jul 7. [Epub ahead of print]

Toxoplasma gondii Uses Unusual Sorting Mechanisms to Deliver Transmembrane Proteins into the Host-Cell Vacuole
Gendrin C, Mercier C, Braun L, Musset K, Dubremetz JF, Cesbron-Delauw MF.

Laboratoire Adaptation et Pathogénie des Micro-organismes, CNRS UMR 5163, Université Joseph Fourier GRENOBLE 1, France.

A critical step in infection by the apicomplexan parasite Toxoplasma gondii, is the formation of a membrane-bound compartment within which the parasite proliferates. This process relies on a set of secretory organelles that discharge their contents into the host-cell upon invasion. Among these organelles, the dense granules are specialized in the export of transmembrane GRA proteins which are major components of the mature parasitophorous vacuole (PV) membrane. How eukaryotic pathogens export and sort membrane-bound proteins destined to the host cell is still poorly understood at the mechanistic level. In the present study, we show that soluble trafficking of the PV-targeted GRA5 transmembrane protein is parasite-specific: when expressed in mammalian cells, GRA5 is targeted to the plasma membrane and behaves as an integral membrane protein with a type I toplogy. We also demonstrate the dual role of the GRA5 N-terminal ectodomain, which is sufficient to prevent membrane integration within the parasite and is essential for both sorting and post-secretory membrane insertion into the vacuolar membrane. These results contrast with the general rule which states that information contained within the cytoplasmic tail and/or the transmembrane domain of integral membrane proteins dictates their cellular localization. They also highlight the diversity of sorting mechanisms that leads to the specialization of secretory processes uniquely adapted to intracellular parasitism.

PMID: 18631244 [PubMed - as supplied by publisher]