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Golgi self-correction generates bioequivalent glycans to preserve cellular homeostasis

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Golgi self-correction generates bioequivalent glycans to 4 preserve cellular homeostasis.pdfAccepted version7.75 MBAdobe PDFView/Open
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Title: Golgi self-correction generates bioequivalent glycans to preserve cellular homeostasis
Authors: Mkhikian, H
Mortales, CL
Zhou, R
Khachikyan, K
Wu, G
Haslam, SM
Kavarian, P
Dell, A
Demetriou, M
Item Type: Journal Article
Abstract: © Mkhikian et al.Essential biological systems employ self-correcting mechanisms to maintain cellular homeostasis. Mammalian cell function is dynamically regulated by the interaction of cell surface galectins with branched N-glycans. Here we report that N-glycan branching deficiency triggers the Golgi to generate bioequivalent N-glycans that preserve galectin-glycoprotein interactions and cellular homeostasis. Galectins bind N-acetyllactosamine (LacNAc) units within N-glycans initiated from UDP-GlcNAc by the medial-Golgi branching enzymes as well as the trans-Golgi poly-LacNAc extension enzyme β1,3-N-acetylglucosaminyltransferase (B3GNT). Marginally reducing LacNAc content by limiting N-glycans to three branches results in T-cell hyperactivity and autoimmunity; yet further restricting branching does not produce a more hyperactive state. Rather, new poly-LacNAc extension by B3GNT maintains galectin binding and immune homeostasis. Poly-LacNAc extension is triggered by redistribution of unused UDP-GlcNAc from the medial to trans-Golgi via inter-cisternal tubules. These data demonstrate the functional equivalency of structurally dissimilar N-glycans and suggest a self-correcting feature of the Golgi that sustains cellular homeostasis.
Issue Date: 8-Jun-2016
Date of Acceptance: 7-Jun-2016
URI: http://hdl.handle.net/10044/1/33848
DOI: https://dx.doi.org/10.7554/eLife.14814
ISSN: 2050-084X
Publisher: eLife Sciences Publications
Journal / Book Title: eLife
Volume: 5
Copyright Statement: Copyright Mkhikian et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Sponsor/Funder: Biotechnology and Biological Sciences Research Council (BBSRC)
Wellcome Trust
Funder's Grant Number: BB/K016164/1
102978/Z/13/Z
Keywords: biochemistry
cell biology
human
mouse
Publication Status: Published
Article Number: e14814
Appears in Collections:Faculty of Natural Sciences



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