Sorting of GPI-anchored proteins at the trypanosome surface is independent of GPI insertion signals

The segregation of glycosylphosphatidylinositol-anchored proteins (GPI-APs) to distinct domains on the plasma membrane of eukaryotic cells is important for their correct cellular function, but the mechanisms by which GPI-APs are sorted are yet to be fully resolved. An extreme example of this is in A...

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Main Authors: Thomas Henry Miller, Sabine Schiessler, Ella Maria Rogerson, Catarina Gadelha
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:The Cell Surface
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Online Access:http://www.sciencedirect.com/science/article/pii/S2468233024000136
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author Thomas Henry Miller
Sabine Schiessler
Ella Maria Rogerson
Catarina Gadelha
author_facet Thomas Henry Miller
Sabine Schiessler
Ella Maria Rogerson
Catarina Gadelha
author_sort Thomas Henry Miller
collection DOAJ
description The segregation of glycosylphosphatidylinositol-anchored proteins (GPI-APs) to distinct domains on the plasma membrane of eukaryotic cells is important for their correct cellular function, but the mechanisms by which GPI-APs are sorted are yet to be fully resolved. An extreme example of this is in African trypanosomes, where the major surface glycoprotein floods the whole cell surface while most GPI-APs are retained in a specialised domain at the base of the flagellum. One possibility is that anchor attachment signals direct differential sorting of proteins. To investigate this, we fused a monomeric reporter to the GPI-anchor insertion signals of trypanosome proteins that are differentially sorted on the plasma membrane. Fusions were correctly anchored by GPI, post-translationally modified, and routed to the plasma membrane, but this delivery was independent of retained signals upstream of the ω site. Instead, ω−minus signal strength appears key to efficacy of GPI addition and to GPI-AP cellular level. Thus, at least in this system, sorting is not encoded at the time of GPI anchor addition or in the insertion sequence retained in processed proteins. We discuss these findings in the context of previously proposed models for sorting mechanisms in trypanosomes.
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spelling doaj-art-ff3e7e1fc68243b29fa4f3eccf10cc6f2024-12-12T05:22:20ZengElsevierThe Cell Surface2468-23302024-12-0112100131Sorting of GPI-anchored proteins at the trypanosome surface is independent of GPI insertion signalsThomas Henry Miller0Sabine Schiessler1Ella Maria Rogerson2Catarina Gadelha3School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UKSchool of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UKSchool of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UKCorresponding author.; School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UKThe segregation of glycosylphosphatidylinositol-anchored proteins (GPI-APs) to distinct domains on the plasma membrane of eukaryotic cells is important for their correct cellular function, but the mechanisms by which GPI-APs are sorted are yet to be fully resolved. An extreme example of this is in African trypanosomes, where the major surface glycoprotein floods the whole cell surface while most GPI-APs are retained in a specialised domain at the base of the flagellum. One possibility is that anchor attachment signals direct differential sorting of proteins. To investigate this, we fused a monomeric reporter to the GPI-anchor insertion signals of trypanosome proteins that are differentially sorted on the plasma membrane. Fusions were correctly anchored by GPI, post-translationally modified, and routed to the plasma membrane, but this delivery was independent of retained signals upstream of the ω site. Instead, ω−minus signal strength appears key to efficacy of GPI addition and to GPI-AP cellular level. Thus, at least in this system, sorting is not encoded at the time of GPI anchor addition or in the insertion sequence retained in processed proteins. We discuss these findings in the context of previously proposed models for sorting mechanisms in trypanosomes.http://www.sciencedirect.com/science/article/pii/S2468233024000136Cell surface receptorGPI anchorSurfeomeESPESAGGPI-AP
spellingShingle Thomas Henry Miller
Sabine Schiessler
Ella Maria Rogerson
Catarina Gadelha
Sorting of GPI-anchored proteins at the trypanosome surface is independent of GPI insertion signals
The Cell Surface
Cell surface receptor
GPI anchor
Surfeome
ESP
ESAG
GPI-AP
title Sorting of GPI-anchored proteins at the trypanosome surface is independent of GPI insertion signals
title_full Sorting of GPI-anchored proteins at the trypanosome surface is independent of GPI insertion signals
title_fullStr Sorting of GPI-anchored proteins at the trypanosome surface is independent of GPI insertion signals
title_full_unstemmed Sorting of GPI-anchored proteins at the trypanosome surface is independent of GPI insertion signals
title_short Sorting of GPI-anchored proteins at the trypanosome surface is independent of GPI insertion signals
title_sort sorting of gpi anchored proteins at the trypanosome surface is independent of gpi insertion signals
topic Cell surface receptor
GPI anchor
Surfeome
ESP
ESAG
GPI-AP
url http://www.sciencedirect.com/science/article/pii/S2468233024000136
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AT sabineschiessler sortingofgpianchoredproteinsatthetrypanosomesurfaceisindependentofgpiinsertionsignals
AT ellamariarogerson sortingofgpianchoredproteinsatthetrypanosomesurfaceisindependentofgpiinsertionsignals
AT catarinagadelha sortingofgpianchoredproteinsatthetrypanosomesurfaceisindependentofgpiinsertionsignals