NDLI: Human UDP-galactose 4′-epimerase (GALE) is required for cell-surface glycome structure and function

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Human UDP-galactose 4′-epimerase (GALE) is required for cell-surface glycome structure and function

Content Provider	Scilit
Author	Broussard, Alex Florwick, Alyssa Desbiens, Chelsea Nischan, Nicole Robertson, Corrina Guan, Ziqiang Kohler, Jennifer J. Wells, Lance Boyce, Michael
Copyright Year	2019
Description	Journal: Journal of Biological Chemistry Glycan biosynthesis relies on nucleotide sugars (NSs), abundant metabolites that serve as monosaccharide donors for glycosyltransferases.In vivo, signal-dependent fluctuations in NS levels are required to maintain normal cell physiology and are dysregulated in disease. However, how mammalian cells regulate NS levels and pathway flux remains largely uncharacterized. To address this knowledge gap, here we examined UDP-galactose 4′-epimerase (GALE), which interconverts two pairs of essential NSs. Using immunoblotting, flow cytometry, and LC-MS–based glycolipid and glycan profiling, we found that CRISPR/Cas9-mediatedGALEdeletion in human cells triggers major imbalances in NSs and dramatic changes in glycolipids and glycoproteins, including a subset of integrins and the cell-surface death receptor FS-7-associated surface antigen. In particular, we observed substantial decreases in total sialic acid, galactose, and GalNAc levels in glycans. These changes also directly impacted cell signaling, $asGALE^{−/−}$cells exhibited FS-7-associated surface antigen ligand-induced apoptosis. Our results reveal a role of GALE-mediated NS regulation in death receptor signaling and may have implications for the molecular etiology of illnesses characterized by NS imbalances, including galactosemia and metabolic syndrome.
Related Links	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996900/pdf http://www.jbc.org/content/early/2019/12/09/jbc.RA119.009271.full.pdf
Ending Page	1239
Page Count	15
Starting Page	1225
ISSN	00219258
e-ISSN	1083351X
DOI	10.1074/jbc.ra119.009271
Journal	Journal of Biological Chemistry
Issue Number	5
Volume Number	295
Language	English
Publisher	Elsevier BV
Publisher Date	2020-01-31
Access Restriction	Open
Subject Keyword	Journal: Journal of Biological Chemistry Biochemistry and Molecular Biology Udp-galactose 4′-epimerase (gale) Carbohydrate Metabolism Nucleoside/nucleotide Metabolism
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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