The GalNAc-T Activation Pathway (GALA) is Not a General Mechanism for Regulating Mucin-type O-glycosylation

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2017 Jul 19

PMID 28719662

Citations 7

Authors

Gaetan G Herbomel

Raul E Rojas

Duy T Tran

Monica Ajinkya

Lauren Beck

Lawrence A Tabak

Affiliations

Soon will be listed here.

Abstract

Mucin-type O-glycosylation is initiated by the UDP-GalNAc polypeptide:N-acetylgalactosaminyltransferase (GalNAc-T) family of enzymes. Their activity results in the GalNAc α1-O-Thr/Ser structure, termed the Tn antigen, which is further decorated with additional sugars. In neoplastic cells, the Tn antigen is often overexpressed. Because O-glycosylation is controlled by the activity of GalNAc-Ts, their regulation is of great interest. Previous reports suggest that growth factors, EGF or PDGF, induce Golgi complex-to-endoplasmic reticulum (ER) relocation of both GalNAc-Ts and Tn antigen in HeLa cells, offering a mechanism for Tn antigen overexpression termed "GALA". However, we were unable to reproduce these findings. Upon treatment of HeLa cells with either EGF or PDGF we observed no change in the co-localization of endogenous GalNAc-T1, GalNAc-T2 or Tn antigen with the Golgi complex marker TGN46. There was also no enhancement of localization with the ER marker calnexin. We conclude that growth factors do not cause redistribution of GalNAc-Ts from the Golgi complex to the ER in HeLa cells.

Citing Articles

Molecular Recognition of GalNAc in Mucin-Type O-Glycosylation.

Sanz-Martinez I, Pereira S, Merino P, Corzana F, Hurtado-Guerrero R Acc Chem Res. 2023; 56(5):548-560.

PMID: 36815693 PMC: 9996832. DOI: 10.1021/acs.accounts.2c00723.

Tn Antigen Expression Contributes to an Immune Suppressive Microenvironment and Drives Tumor Growth in Colorectal Cancer.

Cornelissen L, Blanas A, Zaal A, van der Horst J, Kruijssen L, OToole T Front Oncol. 2020; 10:1622.

PMID: 33014816 PMC: 7461972. DOI: 10.3389/fonc.2020.01622.

Directing Traffic: Regulation of COPI Transport by Post-translational Modifications.

Luo P, Boyce M Front Cell Dev Biol. 2019; 7:190.

PMID: 31572722 PMC: 6749011. DOI: 10.3389/fcell.2019.00190.

The GalNAc-T Activation (GALA) Pathway: Drivers and markers.

Chia J, Tay F, Bard F PLoS One. 2019; 14(3):e0214118.

PMID: 30889231 PMC: 6424425. DOI: 10.1371/journal.pone.0214118.

Polypeptide GalNAc-Ts: from redundancy to specificity.

Rivas M, Lira-Navarrete E, Gerken T, Hurtado-Guerrero R Curr Opin Struct Biol. 2019; 56:87-96.

PMID: 30703750 PMC: 6656595. DOI: 10.1016/j.sbi.2018.12.007.

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