Structure and biological function of ENPP6, a choline-specific glycerophosphodiester-phosphodiesterase
Junko Morita1, Kuniyuki Kano2, Kazuki Kato1
1Department of Biological Sciences, Graduate School of Sciences, The University of Tokyo, 2-11-16, Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan.
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.
Related Concept Videos
Structural Protein Function
Structural Protein Function
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity. In bones and teeth, it mineralizes to...
Nuclear Protein Sorting
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Nuclear Export
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
The Early Endosome: Endocytosis of Transferrin
Regulation of Nuclear Protein Sorting


