Golgi self-correction generates bioequivalent glycans to preserve cellular homeostasis
File(s)
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2016-06-08
Date Acceptance
2016-06-07
Citation
eLife, 2016, 5, pp.1-27
ISSN
2050-084X
Publisher
eLife Sciences Publications
Start Page
1
End Page
27
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.
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.
License URL
Sponsor
Biotechnology and Biological Sciences Research Council (BBSRC)
Wellcome Trust
Identifier
https://elifesciences.org/articles/14814
Grant Number
BB/K016164/1
102978/Z/13/Z
Subjects
Science & Technology
Life Sciences & Biomedicine
Biology
Life Sciences & Biomedicine - Other Topics
ASPARAGINE-LINKED OLIGOSACCHARIDES
POLY-N-ACETYLLACTOSAMINE
ADVANCED MALIGNANCIES
SURFACE ORGANIZATION
MULTIPLE-SCLEROSIS
O-GLYCOSYLATION
HIGH-AFFINITY
COMPLEX
MICE
RECEPTOR
Golgi
N-glycosylation
T cell
biochemistry
bioequivalence
cell biology
galectin
human
mouse
self-correction
Animals
Cells, Cultured
Galectins
Glycoproteins
Golgi Apparatus
Homeostasis
Mice
Polysaccharides
Protein Binding
T-Lymphocytes
T-Lymphocytes
Cells, Cultured
Golgi Apparatus
Animals
Mice
Glycoproteins
Polysaccharides
Galectins
Protein Binding
Homeostasis
0601 Biochemistry and Cell Biology
Publication Status
Published
Article Number
e14814
Date Publish Online
2016-06-08