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Tissue-Specific Regulation of HNK-1 Biosynthesis by Bisecting GlcNAc
Haruka Kawade1, Jyoji Morise2, Sushil K Mishra3
1Graduate School of Natural Science and Technology, Gifu University, Gifu 501-1193, Japan.
Molecules (Basel, Switzerland)
|September 10, 2021
Summary
Bisecting GlcNAc, a sugar modification, uniquely regulates Human Natural Killer-1 (HNK-1) epitope synthesis. This sugar inhibits HNK-1 production in the brain but not the kidney, revealing tissue-specific control mechanisms.
Area of Science:
- Glycobiology
- Neuroscience
- Biochemistry
Background:
- Human Natural Killer-1 (HNK-1) is a crucial sulfated glyco-epitope involved in cell adhesion and synaptic functions.
- HNK-1 and its non-sulfated forms are synthesized by homologous glycosyltransferases GlcAT-P (brain) and GlcAT-S (kidney).
- Regulation of these isozymes in vivo remains largely uncharacterized.
Purpose of the Study:
- To investigate the differential regulation of HNK-1 biosynthesis by bisecting GlcNAc in the brain and kidney.
- To elucidate the molecular mechanisms underlying the tissue-specific effects of bisecting GlcNAc on GlcAT-P and GlcAT-S activity.
Main Methods:
- Analysis of HNK-1 expression in mutant mice lacking bisecting GlcNAc.
- In vitro glycosyltransferase activity assays.
- Molecular dynamics simulations of enzyme-substrate interactions.
Main Results:
- Bisecting GlcNAc suppresses HNK-1 expression in the brain but not the kidney.
- In vitro, bisecting GlcNAc inhibits GlcAT-P activity but not GlcAT-S activity.
- Molecular dynamics simulations reveal poor binding of GlcAT-P to bisected substrates, unlike GlcAT-S.
Conclusions:
- Bisecting GlcNAc differentially regulates HNK-1 synthesis in the brain and kidney.
- This study uncovers a novel mechanism for tissue-specific control of HNK-1 biosynthesis by bisecting GlcNAc.
- Distinct substrate binding properties of homologous isozymes GlcAT-P and GlcAT-S explain differential regulation.
Keywords:
N-acetylglucosaminyltransferase III (GnT-III)bisecting GlcNAcglucuronyltransferase P (GlcAT-P)glucuronyltransferase S (GlcAT-S)glycosylationhuman natural killer—1 (HNK-1)More Related Videos
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