To the Surface and Back: Exo- and Endocytic Pathways in Trypanosoma brucei

Link, Fabian; Borges, Alyssa; Jones, Nicholas Blurton; Engstler, Markus

doi:10.3389/fcell.2021.720521

Cited by 29 publications

(24 citation statements)

References 182 publications

(291 reference statements)

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“…It is unclear whether TbKINX1B "Big Eye" phenotypes are due to direct influence on endocytosis or due to a more general disruption of the flagellar pocket region. The difference between the phenotypes produced in PCF and BSF could be due to the efficiency of RNAi, but also to the shorter doubling time in BSF and the increased rate of endoand exocytosis in BSF compared to PCF (for a recent review, see [31]). However, the importance of the more rapid endoexocytotic system in BSF is clearly emphasized by the lethality induced by TbKINX1B RNAi.…”

Section: Tbkinx1b Is Not Essential In Pcf But Is Vital In Bsfmentioning

confidence: 99%

TbKINX1B: a novel BILBO1 partner and an essential protein in bloodstream form Trypanosoma brucei

et al. 2022

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The flagellar pocket (FP) of the pathogen Trypanosoma brucei is an important single copy structure that is formed by the invagination of the pellicular membrane. It is the unique site of endo- and exocytosis and is required for parasite pathogenicity. The FP consists of distinct structural sub-domains with the least explored being the flagellar pocket collar (FPC). TbBILBO1 is the first-described FPC protein of Trypanosoma brucei. It is essential for parasite survival, FP and FPC biogenesis. In this work, we characterize TbKINX1B, a novel TbBILBO1 partner. We demonstrate that TbKINX1B is located on the basal bodies, the microtubule quartet (a set of four microtubules) and the FPC in T. brucei. Down-regulation of TbKINX1B by RNA interference in bloodstream forms is lethal, inducing an overall disturbance in the endomembrane network. In procyclic forms, the RNAi knockdown of TbKINX1B leads to a minor phenotype with a small number of cells displaying epimastigote-like morphologies, with a misplaced kinetoplast. Our results characterize TbKINX1B as the first putative kinesin to be localized both at the basal bodies and the FPC with a potential role in transporting cargo along with the microtubule quartet.

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Section: Tbkinx1b Is Not Essential In Pcf But Is Vital In Bsfmentioning

confidence: 99%

TbKINX1B: a novel BILBO1 partner and an essential protein in bloodstream form Trypanosoma brucei

et al. 2022

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“…Nonetheless, some cells also showed evidence for intracellular staining, with a noticeable posterior-to-anterior gradient in signal, and a concentrated intensity between the nucleus and kinetoplast (Fig 3A, third row). These observations are not contradictory; endosomes servicing the secretory pathway are known to accumulate at the posterior end of the cell [46], making the intracellular localisation of VIVβ8 consistent with it being trafficked to the cell surface. In fact, surface localisation was confirmed by confocal 3D reconstructions of bloodstream-form cells stained with anti-VIVβ8 antibodies, in where orthogonal views show ring-shaped signal representing the cell edges (Fig 3B).…”

Section: Resultsmentioning

confidence: 99%

Vivaxingenes encode highly immunogenic non-variant antigens unique to theTrypanosoma vivaxcell-surface

Romero-Ramirez

Casas-Sánchez

Autheman

et al. 2022

Preprint

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Trypanosoma vivax is a unicellular hemoparasite, and a principal cause of animal African trypanosomiasis (AAT), a vector-borne and potentially fatal disease of livestock across sub-Saharan Africa. Previously, we identified diverse T. vivax-specific genes that were predicted to encode cell surface proteins. Here, we examine the immune responses of naturally and experimentally infected hosts to many of these unique parasite antigens, to identify immunogens that could become vaccine candidates. Immunoprofiling of host serum showed that one particular family (Fam34) elicits a consistent IgG antibody response. This gene family, which we now call Vivaxin, encodes at least 124 transmembrane glycoproteins that display quite distinct expression profiles and patterns of genetic variation. We focused on one gene (viv-β8) that is among the most immunogenic and highly expressed but displays minimal polymorphism. VIVβ8 was localized across the cell body and flagellar membrane, suggesting that vivaxin is substantial family of novel surface proteins. Although vaccination of mice with VIVβ8 adjuvanted with Quil-A elicits a strong, balanced immune response and delays parasite proliferation in some animals, ultimately, it does not prevent disease. However, our phylogenetic analysis shows vivaxin includes other antigens shown to induce immunity against T. vivax. Thus, the introduction of vivaxin represents an important advance in our understanding of the T. vivax cell surface. Besides being a source of proven and promising vaccine antigens, the gene family is clearly an important component of the parasite glycocalyx, with potential to influence the host-parasite interaction.

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“…The high VSG mobility conferred by the GPI-anchor is also essential for antibody clearance. The incessant and directional movement of trypomastigotes generates hydrodynamic flow forces on the cell surface that drag VSG-antibody complexes to the posterior region of the cell ( Engstler et al, 2007 ), where they are internalized through the flagellar pocket by a very efficient endocytosis machinery (reviewed in Overath and Engstler, 2004 ; Link et al, 2021 ). Another important skill for any parasite is nutrient scavenging from the host.…”

Section: Surface Molecules Of the Human Pathogenic Trypanosomatidsmentioning

confidence: 99%

The Glycosylphosphatidylinositol Anchor: A Linchpin for Cell Surface Versatility of Trypanosomatids

Borges

Link

Engstler

et al. 2021

Front. Cell Dev. Biol.

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The use of glycosylphosphatidylinositol (GPI) to anchor proteins to the cell surface is widespread among eukaryotes. The GPI-anchor is covalently attached to the C-terminus of a protein and mediates the protein’s attachment to the outer leaflet of the lipid bilayer. GPI-anchored proteins have a wide range of functions, including acting as receptors, transporters, and adhesion molecules. In unicellular eukaryotic parasites, abundantly expressed GPI-anchored proteins are major virulence factors, which support infection and survival within distinct host environments. While, for example, the variant surface glycoprotein (VSG) is the major component of the cell surface of the bloodstream form of African trypanosomes, procyclin is the most abundant protein of the procyclic form which is found in the invertebrate host, the tsetse fly vector. Trypanosoma cruzi, on the other hand, expresses a variety of GPI-anchored molecules on their cell surface, such as mucins, that interact with their hosts. The latter is also true for Leishmania, which use GPI anchors to display, amongst others, lipophosphoglycans on their surface. Clearly, GPI-anchoring is a common feature in trypanosomatids and the fact that it has been maintained throughout eukaryote evolution indicates its adaptive value. Here, we explore and discuss GPI anchors as universal evolutionary building blocks that support the great variety of surface molecules of trypanosomatids.

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To the Surface and Back: Exo- and Endocytic Pathways in Trypanosoma brucei

Cited by 29 publications

References 182 publications

TbKINX1B: a novel BILBO1 partner and an essential protein in bloodstream form Trypanosoma brucei

TbKINX1B: a novel BILBO1 partner and an essential protein in bloodstream form Trypanosoma brucei

Vivaxingenes encode highly immunogenic non-variant antigens unique to theTrypanosoma vivaxcell-surface

The Glycosylphosphatidylinositol Anchor: A Linchpin for Cell Surface Versatility of Trypanosomatids

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