Abstract

Apicomplexans are obligate intracellular parasites that invade the host cell in an active process that relies on unique secretory organelles (micronemes, rhoptries and dense granules) localized at the apical tip of these highly polarized eukaryotes. In order for the contents of these specialized organelles to reach their final destination, these proteins are sorted post-Golgi and it has been speculated that they pass through endosomal-like compartments (ELCs), where they undergo maturation. Here, we characterize a Toxoplasma gondii homologue of Syntaxin 6 (TgStx6), a well-established marker for the early endosomes and trans Golgi network (TGN) in diverse eukaryotes. Indeed, TgStx6 appears to have a role in the retrograde transport between ELCs, the TGN and the Golgi, because overexpression of TgStx6 results in the development of abnormally shaped parasites with expanded ELCs, a fragmented Golgi and a defect in inner membrane complex maturation. Interestingly, other organelles such as the micronemes, rhoptries and the apicoplast are not affected, establishing the TGN as a major sorting compartment where several transport pathways intersect. It therefore appears that Toxoplasma has retained a plant-like secretory pathway.

Highlights

  • Apicomplexan parasites such as Toxoplasma gondii or Plasmodium spp. cause some of the most devastating diseases in humans and domestic animals

  • Syntaxin 6 is highly conserved in apicomplexan parasites In order to define post-Golgi trafficking steps in T. gondii, we searched for SNAREs that may be implicated in endosomal transport and identified the apicomplexan homologue of Syntaxin 6 (TgStx6, TGME49_300240) as an ideal candidate

  • Its function is slightly different in yeast and plants, it is known to localize to the trans Golgi network (TGN) and EEs [29,31]; neither of these organelles have been convincingly demonstrated in Toxoplasma

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Summary

Introduction

Apicomplexan parasites such as Toxoplasma gondii or Plasmodium spp. cause some of the most devastating diseases in humans and domestic animals. Rab5-GTPases have been shown to play a crucial role in the transport of rhoptry proteins and a subset of micronemal proteins [8], indicating a modulation of the endocytic trafficking pathway in apicomplexans. Endosomes are sorting organelles where secretory and endocytic traffic intersect in diverse eukaryotic phyla [15] They accept and dispatch vesicles from the trans Golgi network (TGN), the plasma membrane and the lysosome. In all cases, micronemal and rhoptry proteins are secreted constitutively into the PV, just as is the case for carboxypeptidase Y in the corresponding yeast mutants [21] This indicates remodelling of the pathways involved in endocytosis and transport to lysosomes to facilitate the specific transport of micronemal and rhoptry proteins to their respective organelles, which might have evolved from lysosomes [22]. Various SNAREs have been well characterized in plants and yeast, but SNAREs have not yet been functionally analysed in apicomplexans

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