PT  - JOURNAL ARTICLE
AU  - Alex Broussard
AU  - Alyssa Florwick
AU  - Chelsea Desbiens
AU  - Nicole Nischan
AU  - Corrina Robertson
AU  - Ziqiang Guan
AU  - Jennifer J. Kohler
AU  - Lance Wells
AU  - Michael Boyce
TI  - The human UDP-galactose 4’-epimerase (GALE) is required for cell surface glycome structure and function
AID  - 10.1101/646794
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 646794
4099  - http://biorxiv.org/content/early/2019/05/23/646794.short
4100  - http://biorxiv.org/content/early/2019/05/23/646794.full
AB  - Glycan biosynthesis relies on nucleotide-sugars (NS), 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, but how mammalian cells regulate NS levels and pathway flux remains largely uncharacterized. To address this knowledge gap, we examined uridine diphosphate (UDP)-galactose 4’-epimerase (GALE), which interconverts two pairs of essential NSs. GALE deletion in human cells triggered major imbalances in its substrate NSs and consequent dramatic changes in glycolipids and glycoproteins, including a subset of integrins and the Fas death receptor. NS dysregulation also directly impacted cell signaling, as GALE−/− cells exhibit Fas hypoglycosylation and hypersensitivity to Fas ligand-induced apoptosis. Our results reveal a new role for GALE-mediated NS regulation in supporting death receptor signaling and may have implications for the molecular etiology of illnesses characterized by NS imbalances, including galactosemia and metabolic syndrome.