Structure and biological function of ENPP6, a choline-specific glycerophosphodiester-phosphodiesterase

Scientific Reports
Junko MoritaJunken Aoki

Abstract

Choline is an essential nutrient for all living cells and is produced extracellularly by sequential degradation of phosphatidylcholine (PC). However, little is known about how choline is produced extracellularly. Here, we report that ENPP6, a choline-specific phosphodiesterase, hydrolyzes glycerophosphocholine (GPC), a degradation product of PC, as a physiological substrate and participates in choline metabolism. ENPP6 is highly expressed in liver sinusoidal endothelial cells and developing oligodendrocytes, which actively incorporate choline and synthesize PC. ENPP6-deficient mice exhibited fatty liver and hypomyelination, well known choline-deficient phenotypes. The choline moiety of GPC was incorporated into PC in an ENPP6-dependent manner both in vivo and in vitro. The crystal structure of ENPP6 in complex with phosphocholine revealed that the choline moiety of the phosphocholine is recognized by a choline-binding pocket formed by conserved aromatic and acidic residues. The present study provides the molecular basis for ENPP6-mediated choline metabolism at atomic, cellular and tissue levels.

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Citations

Mar 16, 2017·The Journal of Biological Chemistry·Alexei GorelikBhushan Nagar
Oct 17, 2017·Glia·Min LiuSanbing Shen
May 3, 2018·The FEBS Journal·Alexei GorelikBhushan Nagar
Dec 24, 2018·American Journal of Physiology. Gastrointestinal and Liver Physiology·Åke Nilsson, Rui-Dong Duan
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Sep 13, 2017·The FEBS Journal·Alexei GorelikBhushan Nagar
Oct 25, 2020·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Tadashi ShinHiroshi Nishina
Feb 23, 2021·JBMR Plus·Scott DillonColin Farquharson
May 8, 2021·Molecular Metabolism·Georgina K C DowsettGiles S H Yeo
Aug 17, 2021·Journal of Agricultural and Food Chemistry·Ying Qi GohYulan Wang
Nov 30, 2021·Journal of Cellular and Molecular Medicine·Katayoon PakravanSadegh Babashah

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Datasets Mentioned

BETA
AB5320
AB5804
and

Methods Mentioned

BETA
electron micrography
protein folding
gel-filtration
PCR

Software Mentioned

PHENIX
XDS
COOT
MOLREP
Phyre

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