Imperial College London
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ProfessorAnneDell

Faculty of Natural Sciences, Department of Life Sciences

Professor of Carbohydrate Bichemistry
 
 
 
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a.dell

 
 
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Location

 

101BSir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Pham:2017:10.1074/jbc.M116.764597,
author = {Pham, ND and Pang, P-C and Krishnamurthy, S and Wands, AM and Grassi, P and Dell, A and Haslam, SM and Kohler, JJ},
doi = {10.1074/jbc.M116.764597},
journal = {Journal of Biological Chemistry},
pages = {9637--9651},
title = {Effects of altered sialic acid biosynthesis on N-linked glycan branching and cell surface interactions},
url = {http://dx.doi.org/10.1074/jbc.M116.764597},
volume = {292},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - GNE myopathy is a rare muscle disorder associated with aging and is related to sporadic inclusion body myositis (sIBM), the most common acquired muscle disease of aging.  While the cause of sIBM is unknown, GNE myopathy is associated with mutations in UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE).  GNE harbors two enzymatic activities required for biosynthesis of sialic acid in mammalian cells.  Mutations to both GNE domains are linked to GNE myopathy.  However, correlation between mutation-associated reductions in sialic acid production and disease severity is imperfect.  To investigate other potential effects of GNE mutations, we compared sialic acid production in cell lines expressing wild-type or mutant forms of GNE. Although we did not detect any differences attributable to disease-associated mutations, lectin binding and mass spectrometry analysis revealed that GNE deficiency is associated with unanticipated effects on the structure of cell-surface glycans. In addition to exhibiting low levels of sialylation, GNE-deficient cells produced distinct N-linked glycan structures with increased branching and extended poly-N-acetyllactosamine (polyLacNAc). GNE deficiency may affect levels of UDP-GlcNAc, a key metabolite in the nutrient-sensing hexosamine biosynthetic pathway, but this modest effect did not fully account for the change in N-linked glycan structure. Further, GNE deficiency and glucose supplementation acted independently and additively to increase N-linked glycan branching. Notably, N-linked glycans produced by GNE-deficient cells displayed enhanced binding to galectin-1, indicating that changes in GNE activity can alter affinity of cell-surface glycoproteins for the galectin lattice. These findings suggest an unanticipated mechanism by which GNE activity might affect signaling through cell-surface receptors.
AU  - Pham,ND
AU  - Pang,P-C
AU  - Krishnamurthy,S
AU  - Wands,AM
AU  - Grassi,P
AU  - Dell,A
AU  - Haslam,SM
AU  - Kohler,JJ
DO  - 10.1074/jbc.M116.764597
EP  - 9651
PY  - 2017///
SN  - 0021-9258
SP  - 9637
TI  - Effects of altered sialic acid biosynthesis on N-linked glycan branching and cell surface interactions
T2  - Journal of Biological Chemistry
UR  - http://dx.doi.org/10.1074/jbc.M116.764597
UR  - http://www.jbc.org/content/early/2017/04/19/jbc.M116.764597.abstract
UR  - http://hdl.handle.net/10044/1/49774
VL  - 292
ER  -
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