Localization of a Trypanosome Peroxin to the Endoplasmic Reticulum

Bauer, Sarah; McQueeney, Kelley E.; Patel, Terral; Morris, Meredith T.

doi:10.1111/jeu.12343

Cited by 7 publications

(10 citation statements)

References 54 publications

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“…This strengthens our theory that matrix proteins are more likely to require a PTS1 or PTS2 to be properly localized than glycosome membrane proteins or complexes that may derive from the likely glycosome biogenesis involving the ER or even the mitochondrion [28,33]. In the case of PEX13.1, the protein is dual localized, and its PTS1, "TKL", is known to be important for its glucose-dependent glycosome localization [34]. We also analyzed the remaining~100 proteins to determine how many possessed domains indicating a role in pathways clearly unrelated to glycosome function.…”

Section: Utilizing the Pts1 Signal Algorithm In Other Datasetssupporting

confidence: 77%

A Global Analysis of Enzyme Compartmentalization to Glycosomes

et al. 2020

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In kinetoplastids, the first seven steps of glycolysis are compartmentalized into a glycosome along with parts of other metabolic pathways. This organelle shares a common ancestor with the better-understood eukaryotic peroxisome. Much of our understanding of the emergence, evolution, and maintenance of glycosomes is limited to explorations of the dixenous parasites, including the enzymatic contents of the organelle. Our objective was to determine the extent that we could leverage existing studies in model kinetoplastids to determine the composition of glycosomes in species lacking evidence of experimental localization. These include diverse monoxenous species and dixenous species with very different hosts. For many of these, genome or transcriptome sequences are available. Our approach initiated with a meta-analysis of existing studies to generate a subset of enzymes with highest evidence of glycosome localization. From this dataset we extracted the best possible glycosome signal peptide identification scheme for in silico identification of glycosomal proteins from any kinetoplastid species. Validation suggested that a high glycosome localization score from our algorithm would be indicative of a glycosomal protein. We found that while metabolic pathways were consistently represented across kinetoplastids, individual proteins within those pathways may not universally exhibit evidence of glycosome localization.

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Section: Utilizing the Pts1 Signal Algorithm In Other Datasetssupporting

confidence: 77%

A Global Analysis of Enzyme Compartmentalization to Glycosomes

et al. 2020

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“…A global analysis of localized protein synthesis also revealed that many PMPs are likely cotranslated at the ER (Jan et al, 2014). Similar observations of PMP cotranslation (Kaewsapsak et al, 2017) and transport from ER to peroxisomes made in substantially divergent species of yeast (Agrawal et al, 2011; Farre et al, 2017; Titorenko and Rachubinski, 1998), plants (Hu et al, 2012), the excavate pathogen Trypanosoma brucei (Bauer et al, 2017; Guther et al, 2014), and mammalian cells (Kim et al, 2006; Mayerhofer et al, 2016) highlight the essential and evolutionarily ancient role of the ER in peroxisome biogenesis in eukaryotic cells.…”

Section: Introductionsupporting

confidence: 54%

ESCRT-III acts in scissioning new peroxisomes from the ER

Mast¹,

Herricks

Strehler³

et al. 2017

Preprint

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Dynamic control of peroxisome proliferation is integral to the peroxisome’s many functions. A breakdown in the ability of cells to form peroxisomes is linked to many human health issues, including defense against infectious agents, cancer, aging, heart disease, obesity and diabetes, and forms the basis of a spectrum of peroxisomal genetic disorders that cause severe neuropathologies. The ER serves as a source for preperoxisomal vesicles (PPVs) that mature into peroxisomes during de novo peroxisome biogenesis and to support growth and division of existing peroxisomes. However, the mechanism of PPV formation and release from the ER remains poorly understood. Here we show that the evolutionarily ancient endosomal sorting complexes required for transport (ESCRT)-III are peroxisome biogenesis factors that function to cleave PPVs budding from the ER into the cytosol. Using comprehensive morphological and genetic assays of peroxisome formation and function we find that absence of ESCRT-III proteins impedes de novo peroxisome formation and results in an aberrant peroxisome population in vivo. Using a cell-free PPV budding assay we show that ESCRT-III proteins Vps20 and Snf7 are required to release PPVs from the ER. ESCRT-III is therefore a positive effector of membrane scission for vesicles budding both away from and towards the cytosol, a finding that has important implications for the evolutionary timing of emergence of peroxisomes and the rest of the internal membrane architecture of the eukaryotic cell.

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“…Additionally, our lab found that TbPEX13.1 localized to the ER in PF T . brucei under low-glucose conditions [ 59 ]. Because peroxins localize to the ER in other organisms during de novo biogenesis, it is interesting to speculate that TbPEX13.1 localizes to foci in the ER where new glycosomes or preglycosomal vesicles bud.…”

Section: Recent Studies Suggest Glycosomes Can Proliferate De Novo Inmentioning

confidence: 99%

“…This may explain why glucose-dependent changes in glycosome composition occur in a time frame consistent with autophagy [ 68 ]. (B) “New” organelles with protein repertoires better suited to the new levels of glucose in the environment can be generated from the ER [ 48 , 49 , 59 , 60 , 68 – 70 ]. (C) Once new glycosomes are generated, they can be maintained through fission [ 26 ].…”

Section: Recent Studies Suggest Glycosomes Can Proliferate De Novo Inmentioning

confidence: 99%

“…In this pathway, TbPEX13.1 and TbPEX16 are first inserted into the ER membrane via TbPEX19 and get incorporated into budding preglycosomal vesicles. Glucose-dependent regulation of glycosome biogenesis could explain why TbPEX13.1 exhibits ER localization under -Glc conditions [ 59 ] and silencing of TbPEX16 and TbPEX19 does not result in a more dramatic reduction of glycosome number in +Glc conditions [ 47 , 48 ]. (B) Growth and division and de novo mechanisms of glycosome biogenesis occur synergistically and the level at which each mechanism contributes is dependent on the absolute level of glucose.–Glc (glucose-poor, < 0.05 mM), +Glc (glucose-rich, ~5 mM).…”

Section: Glycosomes Biogenesis Is Likely Influenced By Extracellular mentioning

confidence: 99%

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Glycosome biogenesis in trypanosomes and the de novo dilemma

Bauer

Morris

2017

PLoS Negl Trop Dis

Self Cite

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Trypanosomatid parasites, including Trypanosoma and Leishmania, are the causative agents of lethal diseases threatening millions of people around the world. These organisms compartmentalize glycolysis in essential, specialized peroxisomes called glycosomes. Peroxisome proliferation can occur through growth and division of existing organelles and de novo biogenesis from the endoplasmic reticulum. The level that each pathway contributes is debated. Current evidence supports the concerted contribution of both mechanisms in an equilibrium that can vary depending on environmental conditions and metabolic requirements of the cell. Homologs of a number of peroxins, the proteins involved in peroxisome biogenesis and matrix protein import, have been identified in T. brucei. Based on these findings, it is widely accepted that glycosomes proliferate through growth and division of existing organelles; however, to our knowledge, a de novo mechanism of biogenesis has not been directly demonstrated. Here, we review recent findings that provide support for the existence of an endoplasmic reticulum (ER)-derived de novo pathway of glycosome biogenesis in T. brucei. Two studies recently identified PEX13.1, a peroxin involved in matrix protein import, in the ER of procyclic form T. brucei. In other eukaryotes, peroxins including PEX13 have been found in the ER of cells undergoing de novo biogenesis of peroxisomes. In addition, PEX16 and PEX19 have been characterized in T. brucei, both of which are important for de novo biogenesis in other eukaryotes. Because glycosomes are rapidly remodeled via autophagy during life cycle differentiation, de novo biogenesis could provide a method of restoring glycosome populations following turnover. Together, the findings we summarize provide support for the hypothesis that glycosome proliferation occurs through growth and division of pre-existing organelles and de novo biogenesis of new organelles from the ER and that the level each mechanism contributes is influenced by glucose availability.

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Localization of a Trypanosome Peroxin to the Endoplasmic Reticulum

Cited by 7 publications

References 54 publications

A Global Analysis of Enzyme Compartmentalization to Glycosomes

A Global Analysis of Enzyme Compartmentalization to Glycosomes

ESCRT-III acts in scissioning new peroxisomes from the ER

Glycosome biogenesis in trypanosomes and the de novo dilemma

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