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

2021 ◽  
Vol 9 ◽  
Author(s):  
Alyssa R. Borges ◽  
Fabian Link ◽  
Markus Engstler ◽  
Nicola G. Jones
Keyword(s):  
Cell Surface ◽  
Building Blocks ◽  
Tsetse Fly ◽  
Surface Glycoprotein ◽  
African Trypanosomes ◽  
Outer Leaflet ◽  
C Terminus ◽  
Wide Range ◽  
Eukaryote Evolution ◽  
Range Of Functions

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.

scholarly journals Sequence Requirements for Trafficking of the CRAM Transmembrane Protein to the Flagellar Pocket of African Trypanosomes

2000 ◽  
Vol 20 (14) ◽  
pp. 5149-5163 ◽  
Author(s):  
Hong Yang ◽  
David G. Russell ◽  
Baijing Zheng ◽  
Manami Eiki ◽  
Mary Gwo-Shu Lee
Keyword(s):  
Amino Acids ◽  
Cell Surface ◽  
Transmembrane Domain ◽  
Transmembrane Protein ◽  
Surface Glycoprotein ◽  
Cell Surface Expression ◽  
Flagellar Pocket ◽  
African Trypanosomes ◽  
Cytoplasmic Extension ◽  
C Terminus

ABSTRACT CRAM is a cysteine-rich acidic transmembrane protein, highly expressed in the procyclic form of Trypanosoma brucei. Cell surface expression of CRAM is restricted to the flagellar pocket of trypanosomes, the only place where receptor mediated endocytosis takes place in the parasite. CRAM can function as a receptor and was hypothesized to be a lipoprotein receptor of trypanosomes. We study mechanisms involved in the presentation and routing of CRAM to the flagellar pocket of insect- and bloodstream-form trypanosomes. By deletional mutagenesis, we found that deleting up to four amino acids from the C terminus of CRAM did not affect the localization of CRAM at the flagellar pocket. Shortening the CRAM protein by 8 and 19 amino acids from the C terminus resulted in the distribution of the CRAM protein in the endoplasmic reticulum (ER) (the CRAM protein is no longer uniquely sequestered at the flagellar pocket). This result indicates that the truncation of the CRAM C terminus affected the transport efficiency of CRAM from the ER to the flagellar pocket. However, when CRAM was truncated between 29 and 40 amino acids from the C terminus, CRAM was not only distributed in the ER but also located to the flagellar pocket and spread to the cell surface and the flagellum. Replacing the CRAM transmembrane domain with the invariant surface glycoprotein 65-derived transmembrane region did not affect the flagellar pocket location of CRAM. These results indicate that the CRAM cytoplasmic extension may exhibit two functional domains: one domain near the C terminus is important for efficient export of CRAM from the ER, while the second domain is of importance for confining CRAM to the flagellar pocket membrane.

scholarly journals Genome maintenance functions of a putative Trypanosoma brucei translesion DNA polymerase include telomere association and a role in antigenic variation

2020 ◽  
Vol 48 (17) ◽  
pp. 9660-9680
Author(s):  
Andrea Zurita Leal ◽  
Marie Schwebs ◽  
Emma Briggs ◽  
Nadine Weisert ◽  
Helena Reis ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Polymerase ◽  
Antigenic Variation ◽  
Nuclear Periphery ◽  
Surface Glycoprotein ◽  
Dual Function ◽  
African Trypanosomes ◽  
Telomeric Sequences ◽  
Wide Range ◽  
Translesion Dna

Abstract Maintenance of genome integrity is critical to guarantee transfer of an intact genome from parent to offspring during cell division. DNA polymerases (Pols) provide roles in both replication of the genome and the repair of a wide range of lesions. Amongst replicative DNA Pols, translesion DNA Pols play a particular role: replication to bypass DNA damage. All cells express a range of translesion Pols, but little work has examined their function in parasites, including whether the enzymes might contribute to host-parasite interactions. Here, we describe a dual function of one putative translesion Pol in African trypanosomes, which we now name TbPolIE. Previously, we demonstrated that TbPolIE is associated with telomeric sequences and here we show that RNAi-mediated depletion of TbPolIE transcripts results in slowed growth, altered DNA content, changes in cell morphology, and increased sensitivity to DNA damaging agents. We also show that TbPolIE displays pronounced localization at the nuclear periphery, and that its depletion leads to chromosome segregation defects and increased levels of endogenous DNA damage. Finally, we demonstrate that TbPolIE depletion leads to deregulation of telomeric variant surface glycoprotein genes, linking the function of this putative translesion DNA polymerase to host immune evasion by antigenic variation.

scholarly journals Intracellular proteoglycans

2004 ◽  
Vol 379 (2) ◽  
pp. 217-227 ◽  
Author(s):  
Svein Olav KOLSET ◽  
Kristian PRYDZ ◽  
Gunnar PEJLER
Keyword(s):  
Extracellular Matrix ◽  
Cell Surface ◽  
Biological Functions ◽  
Functional Studies ◽  
Wide Range ◽  
Intracellular Compartments ◽  
Range Of Functions ◽  
Intracellular Organelles ◽  
Storage Granules ◽  
The Subject

Proteoglycans (PGs) are proteins with glycosaminoglycan chains, are ubiquitously expressed and have a wide range of functions. PGs in the extracellular matrix and on the cell surface have been the subject of extensive structural and functional studies. Less attention has so far been given to PGs located in intracellular compartments, although several reports suggest that these have biological functions in storage granules, the nucleus and other intracellular organelles. The purpose of this review is, therefore, to present some of these studies and to discuss possible functions linked to PGs located in different intracellular compartments. Reference will be made to publications relevant for the topics we present. It is beyond the scope of this review to cover all publications on PGs in intracellular locations.

scholarly journals Expression site attenuation mechanistically links antigenic variation and development in Trypanosoma brucei

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Christopher Batram ◽  
Nicola G Jones ◽  
Christian J Janzen ◽  
Sebastian M Markert ◽  
Markus Engstler
Keyword(s):  
Trypanosoma Brucei ◽  
Histone Methylation ◽  
Antigenic Variation ◽  
Tsetse Fly ◽  
Developmental Competence ◽  
Surface Glycoprotein ◽  
G1 Phase ◽  
African Trypanosomes ◽  
Developmental Progression ◽  
Expression Site

We have discovered a new mechanism of monoallelic gene expression that links antigenic variation, cell cycle, and development in the model parasite Trypanosoma brucei. African trypanosomes possess hundreds of variant surface glycoprotein (VSG) genes, but only one is expressed from a telomeric expression site (ES) at any given time. We found that the expression of a second VSG alone is sufficient to silence the active VSG gene and directionally attenuate the ES by disruptor of telomeric silencing-1B (DOT1B)-mediated histone methylation. Three conserved expression-site-associated genes (ESAGs) appear to serve as signal for ES attenuation. Their depletion causes G1-phase dormancy and reversible initiation of the slender-to-stumpy differentiation pathway. ES-attenuated slender bloodstream trypanosomes gain full developmental competence for transformation to the tsetse fly stage. This surprising connection between antigenic variation and developmental progression provides an unexpected point of attack against the deadly sleeping sickness.

scholarly journals Genome maintenance functions ofTrypanosoma bruceiDNA Polymerase N include telomere association and a role in antigenic variation

2019 ◽  
Author(s):  
Andrea Zurita Leal ◽  
Marie Schwebs ◽  
Emma Briggs ◽  
Helena Reis ◽  
Leandro Lemgruber ◽  
...  
Keyword(s):  
Dna Damage ◽  
Antigenic Variation ◽  
Nuclear Periphery ◽  
Surface Glycoprotein ◽  
Dual Function ◽  
Exogenous Dna ◽  
African Trypanosomes ◽  
Telomeric Sequences ◽  
Wide Range ◽  
Translesion Dna

AbstractMaintenance of genome integrity is critical to guarantee transfer of an intact genome from parent to offspring during cell division. DNA polymerases (Pols) provide roles in both replication of the genome and the repair of a wide range of lesions. Amongst replicative DNA Pols, translesion DNA Pols play a particular role: replication to bypass DNA damage, often at the cost of mutation. All cells express a range of translesion Pols, but little work has examined their function in parasites, including whether the enzymes might contribute to host-parasite interactions. Here, we describe a dual function of translesion PolN in African trypanosomes. Previously we demonstrated that PolN is associated with telomeric sequences and now we show that RNAi-mediated depletion of PolN results in slowed growth, altered DNA content, changes in cell morphology, and increased sensitivity to DNA damaging agents. Depletion of PolN leads to chromosome segregation defects and accumulation of DNA damage. We also show that PolN displays discrete localisation at the nuclear periphery in the absence of exogenous DNA damage. In addition, we demonstrate that PolN depletion leads to deregulation of telomeric variant surface glycoprotein genes, linking the function of this translesion DNA polymerase to host immune evasion by antigenic variation.

The major cell surface glycoprotein procyclin is a receptor for induction of a novel form of cell death in African trypanosomes in vitro

2000 ◽  
Vol 111 (2) ◽  
pp. 333-349 ◽  
Author(s):  
Terry W Pearson ◽  
Robert P Beecroft ◽  
Susan C Welburn ◽  
Stefan Ruepp ◽  
Isabel Roditi ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Surface ◽  
Surface Glycoprotein ◽  
Cell Surface Glycoprotein ◽  
African Trypanosomes

Transport of a lysosomal membrane glycoprotein from the Golgi to endosomes and lysosomes via the cell surface in African trypanosomes

1994 ◽  
Vol 107 (11) ◽  
pp. 3191-3200 ◽  
Author(s):  
M.J. Brickman ◽  
A.E. Balber
Keyword(s):  
Cell Surface ◽  
Core Protein ◽  
Surface Glycoprotein ◽  
Membrane Glycoprotein ◽  
Flagellar Pocket ◽  
African Trypanosomes ◽  
Processing Enzymes ◽  
Cell Surface Biotinylation ◽  
Lysosomal Membrane Glycoprotein ◽  
Endocytic Compartments

gp57/42 is a membrane glycoprotein localized in the trans-Golgi, flagellar pocket region of the cell surface, endosomes and lysosomes of bloodstream forms of Trypanosoma brucei rhodesiense. Pulse-chase immunoprecipitation experiments revealed that gp57/42 acquires a unique N-linked oligosaccharide recognized by the CB1 monoclonal antibody 20–30 minutes after protein synthesis, probably in the trans-Golgi. We refer to gp57/42 molecules that carry the CB1 epitope as CB1-gp. Pulse labeled CB1-gp contained only one core protein, p57, when chase times were 30 minutes or less. As time of chase increased from 30 to 60 minutes, a new polypeptide, p42, appeared in N-glycanase-treated CB1 immunoprecipitates. Since p57 and p42 share 10 of 13 methionyl peptides, we conclude that p42 is a fragment of p57. Cleavage of p57 to p42 was not inhibited when cells were chased in two thiol protease inhibitors or in 3,4-diisocoumarin, but was inhibited by leupeptin. Cell surface biotinylation was used to determine if newly synthesized CB1-gp was transported from the Golgi to the surface. When cells were pulse labeled and chased for 30 minutes, as much as 40% of the radiolabeled CB1-gp could be biotinylated on the cell surface. The amount of CB1-gp that could be biotinylated decreased when chases were extended from 30 to 60 minutes, suggesting that pulse labeled CB1-gp left the surface. In contrast, pulse labeled variant surface glycoprotein molecules continued to accumulate on the surface where they could be biotinylated between 30 and 60 minutes of chase. Biotinylated CB1-gp derived from cells chased for 30 minutes contained p57 but no p42. However, when labeled cells were biotinylated after a 30 minute chase and then incubated another 30 minutes at 37 degrees C, the biotinylated CB1-gp contained both p57 and p42. The p57 in biotinylated CB1-gp was not cleaved to p42 if the additional incubation was done at 4 or 12 degrees C. This suggests that transport to a compartment where processing occurs and/or the processing enzymes are inhibited by low temperature. When surface biotinylation was done after a 60 minute chase, p42 was detected in biotinylated CB1-gp, suggesting that CB1-gp molecules had passed through the processing compartment and then appeared on the cell surface. Thus, a major portion of the newly synthesized CB1-gp is routed from the Golgi to endocytic compartments via the cell surface. In trypanosomes this process involves a unique surface domain, the flagellar pocket.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Discovery of Fibrillar Adhesins across Bacterial Species

2020 ◽  
Author(s):  
Vivian Monzon ◽  
Aleix Lafita ◽  
Alex Bateman
Keyword(s):  
Cell Surface ◽  
Bacterial Species ◽  
Domain Architecture ◽  
Surface Proteins ◽  
Host Cells ◽  
Bacterial Surface ◽  
Bacterial Phyla ◽  
C Terminus ◽  
Wide Range ◽  
Bacterial Proteomes

AbstractBackgroundFibrillar adhesins are long multidomain proteins attached at the cell surface and composed of at least one adhesive domain and multiple tandemly repeated domains, which build an elongated stalk that projects the adhesive domain beyond the bacterial cell surface. They are an important yet understudied class of proteins that mediate interactions of bacteria with their environment. This study aims to characterize fibrillar adhesins in a wide range of bacterial phyla and to identify new fibrillar adhesin-like proteins to improve our understanding of host-bacteria interactions.ResultsBy careful search for fibrillar adhesins in the literature and by computational analysis we identified 75 stalk domains and 24 adhesive domains. Based on the presence of these domains in the UniProt Reference Proteomes database, we identified and analysed 3,388 fibrillar adhesin-like proteins across species of the most common bacterial phyla. We found that the bacterial proteomes with the highest fraction of fibrillar adhesins include several known pathogens. We further enumerate the adhesive and stalk domain combinations found in nature and demonstrate that fibrillar adhesins have complex and variable domain architectures, which differ across species. By analysing the domain architecture of fibrillar adhesins we show that in Gram positive bacteria adhesive domains are mostly positioned at the N-terminus of the protein with the cell surface anchor at the C-terminus, while their positions are more variable in Gram negative bacteria. We provide an open repository of fibrillar adhesin-like proteins and domains to facilitate downstream studies of this class of bacterial surface proteins.ConclusionThis study provides a domain-based characterization of fibrillar adhesins and demonstrates that they are widely found across the main bacterial phyla. We have discovered numerous novel fibrillar adhesins and improved the understanding of how pathogens might adhere to and subsequently invade into host cells.

scholarly journals Discovery of fibrillar adhesins across bacterial species

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Vivian Monzon ◽  
Aleix Lafita ◽  
Alex Bateman
Keyword(s):  
Cell Surface ◽  
Bacterial Species ◽  
Domain Architecture ◽  
Surface Proteins ◽  
Bacterial Surface ◽  
Bacterial Phyla ◽  
Gram Positive Bacteria ◽  
Invasion Mechanisms ◽  
C Terminus ◽  
Wide Range

Abstract Background Fibrillar adhesins are long multidomain proteins that form filamentous structures at the cell surface of bacteria. They are an important yet understudied class of proteins composed of adhesive and stalk domains that mediate interactions of bacteria with their environment. This study aims to characterize fibrillar adhesins in a wide range of bacterial phyla and to identify new fibrillar adhesin-like proteins to improve our understanding of host-bacteria interactions. Results Through careful literature and computational searches, we identified 82 stalk and 27 adhesive domain families in fibrillar adhesins. Based on the presence of these domains in the UniProt Reference Proteomes database, we identified and analysed 3,542 fibrillar adhesin-like proteins across species of the most common bacterial phyla. We further enumerate the adhesive and stalk domain combinations found in nature and demonstrate that fibrillar adhesins have complex and variable domain architectures, which differ across species. By analysing the domain architecture of fibrillar adhesins, we show that in Gram positive bacteria, adhesive domains are mostly positioned at the N-terminus and cell surface anchors at the C-terminus of the protein, while their positions are more variable in Gram negative bacteria. We provide an open repository of fibrillar adhesin-like proteins and domains to enable further studies of this class of bacterial surface proteins. Conclusion This study provides a domain-based characterization of fibrillar adhesins and demonstrates that they are widely found in species across the main bacterial phyla. We have discovered numerous novel fibrillar adhesins and improved our understanding of pathogenic adhesion and invasion mechanisms.

scholarly journals Tsetse Fly Saliva Accelerates the Onset of Trypanosoma brucei Infection in a Mouse Model Associated with a Reduced Host Inflammatory Response

2006 ◽  
Vol 74 (11) ◽  
pp. 6324-6330 ◽  
Author(s):  
Guy Caljon ◽  
Jan Van Den Abbeele ◽  
Benoît Stijlemans ◽  
Marc Coosemans ◽  
Patrick De Baetselier ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Inflammatory Responses ◽  
Blood Feeding ◽  
Immunoglobulin M ◽  
Tsetse Fly ◽  
Surface Glycoprotein ◽  
Tsetse Flies ◽  
Feeding Site ◽  
African Trypanosomes ◽  
Cytokine Tumor Necrosis Factor

ABSTRACT Tsetse flies (Glossina sp.) are the vectors that transmit African trypanosomes, protozoan parasites that cause human sleeping sickness and veterinary infections in the African continent. These blood-feeding dipteran insects deposit saliva at the feeding site that enables the blood-feeding process. Here we demonstrate that tsetse fly saliva also accelerates the onset of a Trypanosoma brucei infection. This effect was associated with a reduced inflammatory reaction at the site of infection initiation (reflected by a decrease of interleukin-6 [IL-6] and IL-12 mRNA) as well as lower serum concentrations of the trypanocidal cytokine tumor necrosis factor. Variant-specific surface glycoprotein-specific antibody isotypes immunoglobulin M (IgM) and IgG2a, implicated in trypanosome clearance, were not suppressed. We propose that tsetse fly saliva accelerates the onset of trypanosome infection by inhibiting local and systemic inflammatory responses involved in parasite control.

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