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The Mammalian UDP‐Galactose 4′‐Epimerase (GalE) Is Required for Cell Surface Glycome Structure and Function
Author(s) -
Florwick Alyssa T,
Broussard Alex,
Desbiens Chelsea,
Nischan Nicole,
Robertson Corrina,
Guan Ziqiang,
Kohler Jennifer,
Wells Lance,
Boyce Michael
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.798.6
Subject(s) - glycosylation , endoplasmic reticulum , biology , n linked glycosylation , nucleotide sugar , unfolded protein response , microbiology and biotechnology , biochemistry , nucleotide , glycoprotein , gene , glycan
Nucleotide‐sugars are required for glycosylation reactions in mammals, but it is largely unknown how their levels are dynamically regulated in response to cellular signals. The UDP‐galactose 4’‐epimerase (GalE) has recently emerged as a potential regulator of nucleotide‐sugar flux in response to stimuli such as feeding, ischemia and endoplasmic reticulum (ER) stress. The importance of this enzyme is underscored by human patients with hypomorphic GalE alleles, constituting a disease termed type III galactosemia. Critically, the molecular underpinnings of galactosemic pathophysiology are unclear. Because it controls the levels of multiple substrates in several signaling contexts, GalE is an ideal candidate for studying the importance of nucleotide‐sugar regulation in both normal and disease physiology. In this work, we generated GalE −/− human cell lines using CRISPR‐Cas9 mutagenesis. We characterized the effects of GalE loss on nucleotide‐sugar metabolism, protein glycosylation, and death receptor function. Our results demonstrate that loss of the GalE enzyme effects dramatic dysfunction in nucleotide‐sugar metabolism along with protein and lipid glycosylation. We have observed mis‐glycosylation of various cell‐surface proteins. GalE −/− human cells exhibit dysregulated cellular signaling, which we hypothesize is due to mis‐glycosylation of cell‐surface receptors. Support or Funding Information Research in the Boyce Lab has been supported by NIH grants R01GM118847 and R01GM117473 and the Rita Allen Foundation Scholars program This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .