Emerging Mechanisms of Endocytosis in Toxoplasma gondii

McGovern, Olivia L.; Rivera-Cuevas, Yolanda; Carruthers, Vern B.

doi:10.3390/life11020084

Cited by 20 publications

(22 citation statements)

References 128 publications

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“…gondii is capable of internalizing host-derived cytosolic proteins [ 3 ]. Once endocytosed, the material is trafficked throughout the endolysosomal system of the parasite and delivered to its lysosomal vacuolar-like compartment (VAC) for degradation by the cysteine protease cathepsin L (TgCPL) [ 4 , 5 ]. However, the molecular mechanisms by which this material is trafficked across the PV membrane (PVM) and is further endocytosed by the parasite remained poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Toxoplasma gondii exploits the host ESCRT machinery for parasite uptake of host cytosolic proteins

et al. 2021

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Toxoplasma gondii is a master manipulator capable of effectively siphoning the resources from the host cell for its intracellular subsistence. However, the molecular underpinnings of how the parasite gains resources from its host remain largely unknown. Residing within a non-fusogenic parasitophorous vacuole (PV), the parasite must acquire resources across the limiting membrane of its replicative niche, which is decorated with parasite proteins including those secreted from dense granules. We discovered a role for the Endosomal Sorting Complex Required for Transport (ESCRT) machinery in host cytosolic protein uptake by T. gondii by disrupting host ESCRT function. We identified the transmembrane dense granule protein TgGRA14, which contains motifs homologous to the late domain motifs of HIV-1 Gag, as a candidate for the recruitment of the host ESCRT machinery to the PV membrane. Using an HIV-1 virus-like particle (VLP) release assay, we found that the motif-containing portion of TgGRA14 is sufficient to substitute for HIV-1 Gag late domain to mediate ESCRT-dependent VLP budding. We also show that TgGRA14 is proximal to and interacts with host ESCRT components and other dense granule proteins during infection. Furthermore, analysis of TgGRA14-deficient parasites revealed a marked reduction in ingestion of a host cytosolic protein compared to WT parasites. Thus, we propose a model in which T. gondii recruits the host ESCRT machinery to the PV where it can interact with TgGRA14 for the internalization of host cytosolic proteins across the PV membrane (PVM). These findings provide new insight into how T. gondii accesses contents of the host cytosol by exploiting a key pathway for vesicular budding and membrane scission.

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Section: Introductionmentioning

confidence: 99%

Toxoplasma gondii exploits the host ESCRT machinery for parasite uptake of host cytosolic proteins

et al. 2021

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“…Different from the cytostome of P. falciparum, T. gondii apparently does not internalize the PV membrane by the micropore [98]. This observation was contradicted by recent studies [99][100][101], in which it has been shown that the micropore can pinch off the PV membrane. Furthermore, it was proposed that T. gondii exploits a trogocytosislike pathway to engulf host Rab small GTPases-marked Golgi or Golgi-associated vesicles, which T. gondii closely resides to, in order to gain sphingolipids [102,103].…”

Section: Toxoplasma Gondiimentioning

confidence: 74%

Trogocytosis in Unicellular Eukaryotes

Nakada‐Tsukui

Nozaki

2021

Cells

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Trogocytosis is a mode of internalization of a part of a live cell by nibbling and is mechanistically distinct from phagocytosis, which implies internalization of a whole cell or a particle. Trogocytosis has been demonstrated in a broad range of cell types in multicellular organisms and is also known to be involved in a plethora of functions. In immune cells, trogocytosis is involved in the “cross-dressing” between antigen presenting cells and T cells, and is thus considered to mediate intercellular communication. On the other hand, trogocytosis has also been reported in a variety of unicellular organisms including the protistan (protozoan) parasite Entamoeba histolytica. E. histolytica ingests human T cell line by trogocytosis and acquires complement resistance and cross-dresses major histocompatibility complex (MHC) class I on the cell surface. Furthermore, trogocytosis and trogocytosis-like phenomena (nibbling of a live cell, not previously described as trogocytosis) have also been reported in other parasitic protists such as Trichomonas, Plasmodium, Toxoplasma, and free-living amoebae. Thus, trogocytosis is conserved in diverse eukaryotic supergroups as a means of intercellular communication. It is depicting the universality of trogocytosis among eukaryotes. In this review, we summarize our current understanding of trogocytosis in unicellular organisms, including the history of its discovery, taxonomical distribution, roles, and molecular mechanisms.

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“…The association with the AP-2 adaptor complex, EPS15/intersectin-1-like proteins, and DrpC could also suggest a role in endocytosis at this site. Endocytosis is still poorly understood in T. gondii , but it is believed to occur at a structure called the micropore ( 26 , 34 ). The IMC suture puncta seem likely to correlate with the micropore, but additional experiments will be necessary to confirm this and a direct role in endocytosis at this site.…”

Section: Discussionmentioning

confidence: 99%