Pothukuchi, Prathyush ORCID: 0000-0002-6242-2319, Agliarulo, Ilenia, Pirozzi, Marinella, Rizzo, Riccardo ORCID: 0000-0002-5716-9195, Russo, Domenico, Turacchio, Gabriele, Nuechel, Julian, Yang, Jia-Shu, Gehin, Charlotte ORCID: 0000-0003-1164-2968, Capolupo, Laura, Hernandez-Corbacho, Maria Jose, Biswas, Ansuman, Vanacore, Giovanna, Dathan, Nina, Nitta, Takahiro, Henklein, Petra, Thattai, Mukund, Inokuchi, Jin-Ichi, Hsu, Victor W., Plomann, Markus, Obeid, Lina M., Hannun, Yusuf A., Luini, Alberto, D'Angelo, Giovanni and Parashuraman, Seetharaman (2021). GRASP55 regulates intra-Golgi localization of glycosylation enzymes to control glycosphingolipid biosynthesis. Embo J., 40 (20). HOBOKEN: WILEY. ISSN 1460-2075

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Abstract

The Golgi apparatus, the main glycosylation station of the cell, consists of a stack of discontinuous cisternae. Glycosylation enzymes are usually concentrated in one or two specific cisternae along the cis-trans axis of the organelle. How such compartmentalized localization of enzymes is achieved and how it contributes to glycosylation are not clear. Here, we show that the Golgi matrix protein GRASP55 directs the compartmentalized localization of key enzymes involved in glycosphingolipid (GSL) biosynthesis. GRASP55 binds to these enzymes and prevents their entry into COPI-based retrograde transport vesicles, thus concentrating them in the trans-Golgi. In genome-edited cells lacking GRASP55, or in cells expressing mutant enzymes without GRASP55 binding sites, these enzymes relocate to the cis-Golgi, which affects glycosphingolipid biosynthesis by changing flux across metabolic branch points. These findings reveal a mechanism by which a matrix protein regulates polarized localization of glycosylation enzymes in the Golgi and controls competition in glycan biosynthesis.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Pothukuchi, PrathyushUNSPECIFIEDorcid.org/0000-0002-6242-2319UNSPECIFIED
Agliarulo, IleniaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pirozzi, MarinellaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rizzo, RiccardoUNSPECIFIEDorcid.org/0000-0002-5716-9195UNSPECIFIED
Russo, DomenicoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Turacchio, GabrieleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuechel, JulianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yang, Jia-ShuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gehin, CharlotteUNSPECIFIEDorcid.org/0000-0003-1164-2968UNSPECIFIED
Capolupo, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hernandez-Corbacho, Maria JoseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Biswas, AnsumanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vanacore, GiovannaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dathan, NinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nitta, TakahiroUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Henklein, PetraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thattai, MukundUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Inokuchi, Jin-IchiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hsu, Victor W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Plomann, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Obeid, Lina M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hannun, Yusuf A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Luini, AlbertoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
D'Angelo, GiovanniUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Parashuraman, SeetharamanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-601636
DOI: 10.15252/embj.2021107766
Journal or Publication Title: Embo J.
Volume: 40
Number: 20
Date: 2021
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1460-2075
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
COPI VESICLES; TRAFFICKING; STACKING; PROTEINS; GLYCOSYLTRANSFERASES; GLUCOSYLCERAMIDE; SPHINGOLIPIDS; METABOLISM; EXPRESSION; RETENTIONMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60163

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