Cargando…

GOLPH3 and GOLPH3L are broad-spectrum COPI adaptors for sorting into intra-Golgi transport vesicles

The fidelity of Golgi glycosylation is, in part, ensured by compartmentalization of enzymes within the stack. The COPI adaptor GOLPH3 has been shown to interact with the cytoplasmic tails of a subset of Golgi enzymes and direct their retention. However, other mechanisms of retention, and other roles...

Descripción completa

Detalles Bibliográficos
Autores principales: Welch, Lawrence G., Peak-Chew, Sew-Yeu, Begum, Farida, Stevens, Tim J., Munro, Sean
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421267/
https://www.ncbi.nlm.nih.gov/pubmed/34473204
http://dx.doi.org/10.1083/jcb.202106115
_version_ 1783749044813692928
author Welch, Lawrence G.
Peak-Chew, Sew-Yeu
Begum, Farida
Stevens, Tim J.
Munro, Sean
author_facet Welch, Lawrence G.
Peak-Chew, Sew-Yeu
Begum, Farida
Stevens, Tim J.
Munro, Sean
author_sort Welch, Lawrence G.
collection PubMed
description The fidelity of Golgi glycosylation is, in part, ensured by compartmentalization of enzymes within the stack. The COPI adaptor GOLPH3 has been shown to interact with the cytoplasmic tails of a subset of Golgi enzymes and direct their retention. However, other mechanisms of retention, and other roles for GOLPH3, have been proposed, and a comprehensive characterization of the clientele of GOLPH3 and its paralogue GOLPH3L is lacking. GOLPH3’s role is of particular interest as it is frequently amplified in several solid tumor types. Here, we apply two orthogonal proteomic methods to identify GOLPH3+3L clients and find that they act in diverse glycosylation pathways or have other roles in the Golgi. Binding studies, bioinformatics, and a Golgi retention assay show that GOLPH3+3L bind the cytoplasmic tails of their clients through membrane-proximal positively charged residues. Furthermore, deletion of GOLPH3+3L causes multiple defects in glycosylation. Thus, GOLPH3+3L are major COPI adaptors that impinge on most, if not all, of the glycosylation pathways of the Golgi.
format Online
Article
Text
id pubmed-8421267
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-84212672021-09-08 GOLPH3 and GOLPH3L are broad-spectrum COPI adaptors for sorting into intra-Golgi transport vesicles Welch, Lawrence G. Peak-Chew, Sew-Yeu Begum, Farida Stevens, Tim J. Munro, Sean J Cell Biol Article The fidelity of Golgi glycosylation is, in part, ensured by compartmentalization of enzymes within the stack. The COPI adaptor GOLPH3 has been shown to interact with the cytoplasmic tails of a subset of Golgi enzymes and direct their retention. However, other mechanisms of retention, and other roles for GOLPH3, have been proposed, and a comprehensive characterization of the clientele of GOLPH3 and its paralogue GOLPH3L is lacking. GOLPH3’s role is of particular interest as it is frequently amplified in several solid tumor types. Here, we apply two orthogonal proteomic methods to identify GOLPH3+3L clients and find that they act in diverse glycosylation pathways or have other roles in the Golgi. Binding studies, bioinformatics, and a Golgi retention assay show that GOLPH3+3L bind the cytoplasmic tails of their clients through membrane-proximal positively charged residues. Furthermore, deletion of GOLPH3+3L causes multiple defects in glycosylation. Thus, GOLPH3+3L are major COPI adaptors that impinge on most, if not all, of the glycosylation pathways of the Golgi. Rockefeller University Press 2021-09-02 /pmc/articles/PMC8421267/ /pubmed/34473204 http://dx.doi.org/10.1083/jcb.202106115 Text en © 2021 MRC Laboratory of Molecular Biology https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Welch, Lawrence G.
Peak-Chew, Sew-Yeu
Begum, Farida
Stevens, Tim J.
Munro, Sean
GOLPH3 and GOLPH3L are broad-spectrum COPI adaptors for sorting into intra-Golgi transport vesicles
title GOLPH3 and GOLPH3L are broad-spectrum COPI adaptors for sorting into intra-Golgi transport vesicles
title_full GOLPH3 and GOLPH3L are broad-spectrum COPI adaptors for sorting into intra-Golgi transport vesicles
title_fullStr GOLPH3 and GOLPH3L are broad-spectrum COPI adaptors for sorting into intra-Golgi transport vesicles
title_full_unstemmed GOLPH3 and GOLPH3L are broad-spectrum COPI adaptors for sorting into intra-Golgi transport vesicles
title_short GOLPH3 and GOLPH3L are broad-spectrum COPI adaptors for sorting into intra-Golgi transport vesicles
title_sort golph3 and golph3l are broad-spectrum copi adaptors for sorting into intra-golgi transport vesicles
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421267/
https://www.ncbi.nlm.nih.gov/pubmed/34473204
http://dx.doi.org/10.1083/jcb.202106115
work_keys_str_mv AT welchlawrenceg golph3andgolph3larebroadspectrumcopiadaptorsforsortingintointragolgitransportvesicles
AT peakchewsewyeu golph3andgolph3larebroadspectrumcopiadaptorsforsortingintointragolgitransportvesicles
AT begumfarida golph3andgolph3larebroadspectrumcopiadaptorsforsortingintointragolgitransportvesicles
AT stevenstimj golph3andgolph3larebroadspectrumcopiadaptorsforsortingintointragolgitransportvesicles
AT munrosean golph3andgolph3larebroadspectrumcopiadaptorsforsortingintointragolgitransportvesicles