Life Stage-Specific Cargo Receptors Facilitate Glycosylphosphatidylinositol-Anchored Surface Coat Protein Transport in <named-content content-type="genus-species">Trypanosoma brucei</named-content>

ABSTRACT The critical virulence factor of bloodstream-form Trypanosoma brucei is the glycosylphosphatidylinositol (GPI)-anchored variant surface glycoprotein (VSG). Endoplasmic reticulum (ER) exit of VSG is GPI dependent and relies on a discrete subset of COPII machinery (TbSec23.2/TbSec24.1). In ot...

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Autores principales:	Emilia K. Kruzel, George P. Zimmett, James D. Bangs
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	COPII ER exit GPI anchor Trypanosoma cargo receptor p24 Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/046dc2cb82e449bfa75383f21a214d7f
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spelling	oai:doaj.org-article:046dc2cb82e449bfa75383f21a214d7f2021-11-15T15:22:04ZLife Stage-Specific Cargo Receptors Facilitate Glycosylphosphatidylinositol-Anchored Surface Coat Protein Transport in <named-content content-type="genus-species">Trypanosoma brucei</named-content>10.1128/mSphere.00282-172379-5042https://doaj.org/article/046dc2cb82e449bfa75383f21a214d7f2017-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00282-17https://doaj.org/toc/2379-5042ABSTRACT The critical virulence factor of bloodstream-form Trypanosoma brucei is the glycosylphosphatidylinositol (GPI)-anchored variant surface glycoprotein (VSG). Endoplasmic reticulum (ER) exit of VSG is GPI dependent and relies on a discrete subset of COPII machinery (TbSec23.2/TbSec24.1). In other systems, p24 transmembrane adaptor proteins selectively recruit GPI-anchored cargo into nascent COPII vesicles. Trypanosomes have eight putative p24s (TbERP1 to TbERP8) that are constitutively expressed at the mRNA level. However, only four TbERP proteins (TbERP1, -2, -3, and -8) are detectable in bloodstream-form parasites. All four colocalize to ER exit sites, are required for efficient GPI-dependent ER exit, and are interdependent for steady-state stability. These results suggest shared function as an oligomeric ER GPI-cargo receptor. This cohort also mediates rapid forward trafficking of the soluble lysosomal hydrolase TbCatL. Procyclic insect-stage trypanosomes have a distinct surface protein, procyclin, bearing a different GPI anchor structure. A separate cohort of TbERP proteins (TbERP1, -2, -4, and -8) are expressed in procyclic parasites and also function in GPI-dependent ER exit. Collectively, these results suggest developmentally regulated TbERP cohorts, likely in obligate assemblies, that may recognize stage-specific GPI anchors to facilitate GPI-cargo trafficking throughout the parasite life cycle. IMPORTANCE African trypanosomes are protozoan parasites that cause African sleeping sickness. Critical to the success of the parasite is the variant surface glycoprotein (VSG), which covers the parasite cell surface and which is essential for evasion of the host immune system. VSG is membrane bound by a glycolipid (GPI) anchor that is attached in the earliest compartment of the secretory pathway, the endoplasmic reticulum (ER). We have previously shown that the anchor acts as a positive forward trafficking signal for ER exit, implying a cognate receptor mechanism for GPI recognition and loading in coated cargo vesicles leaving the ER. Here, we characterize a family of small transmembrane proteins that act at adaptors for this process. This work adds to our understanding of general GPI function in eukaryotic cells and specifically in the synthesis and transport of the critical virulence factor of pathogenic African trypanosomes.Emilia K. KruzelGeorge P. ZimmettJames D. BangsAmerican Society for MicrobiologyarticleCOPIIER exitGPI anchorTrypanosomacargo receptorp24MicrobiologyQR1-502ENmSphere, Vol 2, Iss 4 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	COPII ER exit GPI anchor Trypanosoma cargo receptor p24 Microbiology QR1-502
spellingShingle	COPII ER exit GPI anchor Trypanosoma cargo receptor p24 Microbiology QR1-502 Emilia K. Kruzel George P. Zimmett James D. Bangs Life Stage-Specific Cargo Receptors Facilitate Glycosylphosphatidylinositol-Anchored Surface Coat Protein Transport in <named-content content-type="genus-species">Trypanosoma brucei</named-content>
description	ABSTRACT The critical virulence factor of bloodstream-form Trypanosoma brucei is the glycosylphosphatidylinositol (GPI)-anchored variant surface glycoprotein (VSG). Endoplasmic reticulum (ER) exit of VSG is GPI dependent and relies on a discrete subset of COPII machinery (TbSec23.2/TbSec24.1). In other systems, p24 transmembrane adaptor proteins selectively recruit GPI-anchored cargo into nascent COPII vesicles. Trypanosomes have eight putative p24s (TbERP1 to TbERP8) that are constitutively expressed at the mRNA level. However, only four TbERP proteins (TbERP1, -2, -3, and -8) are detectable in bloodstream-form parasites. All four colocalize to ER exit sites, are required for efficient GPI-dependent ER exit, and are interdependent for steady-state stability. These results suggest shared function as an oligomeric ER GPI-cargo receptor. This cohort also mediates rapid forward trafficking of the soluble lysosomal hydrolase TbCatL. Procyclic insect-stage trypanosomes have a distinct surface protein, procyclin, bearing a different GPI anchor structure. A separate cohort of TbERP proteins (TbERP1, -2, -4, and -8) are expressed in procyclic parasites and also function in GPI-dependent ER exit. Collectively, these results suggest developmentally regulated TbERP cohorts, likely in obligate assemblies, that may recognize stage-specific GPI anchors to facilitate GPI-cargo trafficking throughout the parasite life cycle. IMPORTANCE African trypanosomes are protozoan parasites that cause African sleeping sickness. Critical to the success of the parasite is the variant surface glycoprotein (VSG), which covers the parasite cell surface and which is essential for evasion of the host immune system. VSG is membrane bound by a glycolipid (GPI) anchor that is attached in the earliest compartment of the secretory pathway, the endoplasmic reticulum (ER). We have previously shown that the anchor acts as a positive forward trafficking signal for ER exit, implying a cognate receptor mechanism for GPI recognition and loading in coated cargo vesicles leaving the ER. Here, we characterize a family of small transmembrane proteins that act at adaptors for this process. This work adds to our understanding of general GPI function in eukaryotic cells and specifically in the synthesis and transport of the critical virulence factor of pathogenic African trypanosomes.
format	article
author	Emilia K. Kruzel George P. Zimmett James D. Bangs
author_facet	Emilia K. Kruzel George P. Zimmett James D. Bangs
author_sort	Emilia K. Kruzel
title	Life Stage-Specific Cargo Receptors Facilitate Glycosylphosphatidylinositol-Anchored Surface Coat Protein Transport in <named-content content-type="genus-species">Trypanosoma brucei</named-content>
title_short	Life Stage-Specific Cargo Receptors Facilitate Glycosylphosphatidylinositol-Anchored Surface Coat Protein Transport in <named-content content-type="genus-species">Trypanosoma brucei</named-content>
title_full	Life Stage-Specific Cargo Receptors Facilitate Glycosylphosphatidylinositol-Anchored Surface Coat Protein Transport in <named-content content-type="genus-species">Trypanosoma brucei</named-content>
title_fullStr	Life Stage-Specific Cargo Receptors Facilitate Glycosylphosphatidylinositol-Anchored Surface Coat Protein Transport in <named-content content-type="genus-species">Trypanosoma brucei</named-content>
title_full_unstemmed	Life Stage-Specific Cargo Receptors Facilitate Glycosylphosphatidylinositol-Anchored Surface Coat Protein Transport in <named-content content-type="genus-species">Trypanosoma brucei</named-content>
title_sort	life stage-specific cargo receptors facilitate glycosylphosphatidylinositol-anchored surface coat protein transport in <named-content content-type="genus-species">trypanosoma brucei</named-content>
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/046dc2cb82e449bfa75383f21a214d7f
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Life Stage-Specific Cargo Receptors Facilitate Glycosylphosphatidylinositol-Anchored Surface Coat Protein Transport in <named-content content-type="genus-species">Trypanosoma brucei</named-content>

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