A Balance between Transmembrane-Mediated ER/Golgi Retention and Forward Trafficking Signals in Glycophorin-Anion Exchanger-1 Interaction.

Content Provider	Europe PMC
Author	Hsu, Kate Lee, Ting-Ying Lin, Jian-Yi Chen, Pin-Lung
Editor	Kaestner, Lars Bogdanova, Anna
Copyright Year	2022
Abstract	Anion exchanger-1 (AE1) is the main erythroid Cl−/HCO3− transporter that supports CO2 transport. Glycophorin A (GPA), a component of the AE1 complexes, facilitates AE1 expression and anion transport, but Glycophorin B (GPB) does not. Here, we dissected the structural components of GPA/GPB involved in glycophorin-AE1 trafficking by comparing them with three GPB variants—GPBhead (lacking the transmembrane domain [TMD]), GPBtail (mainly the TMD), and GP.Mur (glycophorin B-A-B hybrid). GPB-derived GP.Mur bears an O-glycopeptide that encompasses the R18 epitope, which is present in GPA but not GPB. By flow cytometry, AE1 expression in the control erythrocytes increased with the GPA-R18 expression; GYP.Mur+/+ erythrocytes bearing both GP.Mur and GPA expressed more R18 epitopes and more AE1 proteins. In contrast, heterologously expressed GPBtail and GPB were predominantly localized in the Golgi apparatus of HEK-293 cells, whereas GBhead was diffuse throughout the cytosol, suggesting that glycophorin transmembrane encoded an ER/Golgi retention signal. AE1 coexpression could reduce the ER/Golgi retention of GPB, but not of GPBtail or GPBhead. Thus, there are forward-trafficking and transmembrane-driven ER/Golgi retention signals encoded in the glycophorin sequences. How the balance between these opposite trafficking signals could affect glycophorin sorting into AE1 complexes and influence erythroid anion transport remains to be explored.
Journal	Cells
Volume Number	11
PubMed Central reference number	PMC9653601
Issue Number	21
PubMed reference number	36359907
e-ISSN	20734409
DOI	10.3390/cells11213512
Language	English
Publisher	MDPI
Publisher Date	2022-11-06
Access Restriction	Open
Rights License	Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). © 2022 by the authors.
Subject Keyword	red blood cells (RBCs; erythrocytes) anion exchanger-1 (AE1; band 3; SLC4A1) glycophorin A (GPA) glycophorin B (GPB) GP.Mur (Miltenberger subtype III; Mi.III) ER/Golgi retention oligomerization transmembrane domain (TMD) trafficking membrane protein
Content Type	Text
Resource Type	Article
Subject	Biochemistry, Genetics and Molecular Biology