Toxoplasma Retromer Is Here to Stay

Abstract

How the protozoan pathogen Toxoplasma gondii and related parasites shuttle proteins through their intricate system of endomembranous compartments remains unclear. Sangaré et al. show that the Toxoplasma retromer complex is essential for parasite viability through its role in protein targeting to multiple locales and its interactions with newly identified partners.

Keywords: membrane; parasite; protein; targeting; trafficking.

Figure 1. Working model for protein targeting within the exo/endocytic system of Toxoplasma

(1) The endosomal sorting receptor TgSORTLR guides microneme and rhoptry proteins through the endosome-like compartments (ELCs), where proteolytic processing may occur before delivery to the microneme (MIC) and rhoptry (ROP) organelles. Subsequent rounds of microneme and rhoptry biogenesis are sustained by retromer-mediated recycling of TgSORTLR from the ELCs to the trans-Golgi network. (2) Retromer also regulates the secretion of dense granules (DGs), although it is unclear if this effect is direct. (3) TgHP03 and potentially other plasma membrane proteins are recycled from internal vesicular structures (here presumed to involve ELCs) in a retromer-dependent manner. Rab5B may drive this process similar to its plant ortholog ARA6. (4) Retromer interaction with Rab11B and TgHP12, a potential partner of Rab11B, suggests a role for retromer in inner membrane complex (IMC) biogenesis. (5) Depletion of retromer does not result in apparent degradation of retromer cargoes, suggesting that vacuolar compartment/plant-like vacuole (VAC) targeting is not the default pathway in the Toxoplasma endocytic system. If ingested host material traverses the ELCs on its way to the VAC, this may occur in a receptor-mediated manner similar to microneme and rhoptry sorting.