Analysis of the biogenesis of heparan sulfate acetyl-CoA:alpha-glucosaminide N-acetyltransferase provides insights into the mechanism underlying its complete deficiency in mucopolysaccharidosis IIIC.

The Journal of Biological Chemistry
Stéphanie DurandAlexey V Pshezhetsky

Abstract

Heparan sulfate acetyl-CoA:α-glucosaminide N-acetyltransferase (HGSNAT) catalyzes the transmembrane acetylation of heparan sulfate in lysosomes required for its further catabolism. Inherited deficiency of HGSNAT in humans results in lysosomal storage of heparan sulfate and causes the severe neurodegenerative disease, mucopolysaccharidosis IIIC (MPS IIIC). Previously we have cloned the HGSNAT gene, identified molecular defects in MPS IIIC patients, and found that all missense mutations prevented normal folding and trafficking of the enzyme. Therefore characterization of HGSNAT biogenesis and intracellular trafficking became of central importance for understanding the molecular mechanism underlying the disease and developing future therapies. In the current study we show that HGSNAT is synthesized as a catalytically inactive 77-kDa precursor that is transported to the lysosomes via an adaptor protein-mediated pathway that involves conserved tyrosine- and dileucine-based lysosomal targeting signals in its C-terminal cytoplasmic domain with a contribution from a dileucine-based signal in the N-terminal cytoplasmic loop. In the lysosome, the precursor is cleaved into a 29-kDa N-terminal α-chain and a 48-kDa C-terminal β-chain, and a...Continue Reading

References

May 1, 1989·Journal of Cellular Biochemistry·A H Erickson
Sep 5, 1986·Science·K J Bame, L H Rome
Jun 1, 1995·Trends in Neurosciences·W N Green, N S Millar
Aug 31, 1993·Biochemical and Biophysical Research Communications·A V Pshezhetsky, M Potier
Aug 5, 1999·The Biochemical Journal·M RamjeesinghC E Bear
Apr 8, 2000·Current Opinion in Structural Biology·B M PearseD J Owen
Jul 6, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·E C Dell'AngelicaJ S Bonifacino
Feb 15, 2001·The New England Journal of Medicine·E D KakkisE F Neufeld
Mar 26, 2003·Annual Review of Biochemistry·Juan S Bonifacino, Linton M Traub
Nov 1, 2005·The Journal of Biological Chemistry·Kirill KiselyovAbigail Soyombo
Nov 21, 2007·Molecular Genetics and Metabolism·G J G RuijterF A Wijburg
Oct 22, 2008·Nature Methods·Danielle L SwaneyJoshua J Coon
Dec 11, 2008·Journal of Proteomics·John W CallahanDon J Mahuran
Jan 17, 2009·Biochimica Et Biophysica Acta·Raquel RuivoBruno Gasnier
Feb 3, 2009·Proceedings of the National Academy of Sciences of the United States of America·Arianna RathCharles M Deber
Aug 13, 2009·Nature Reviews. Molecular Cell Biology·Paul Saftig, Judith Klumperman
Sep 15, 2009·Trends in Biochemical Sciences·Peter M JonesAnthony M George
Oct 14, 2009·PloS One·Matthew FeldhammerAlexey V Pshezhetsky
Jan 21, 2010·Physiological Reviews·Hiroshi HibinoYoshihisa Kurachi

❮ Previous
Next ❯

Citations

Apr 24, 2013·Nature Reviews. Molecular Cell Biology·Carmine SettembreAndrea Ballabio
Oct 21, 2011·Biochemistry Research International·Maria Francisca CoutinhoSandra Alves
Dec 11, 2014·Orphanet Journal of Rare Diseases·Liliana MatosLluïsa Vilageliu
Jan 9, 2015·Brain : a Journal of Neurology·Carla MartinsAlexey V Pshezhetsky
Mar 23, 2013·Diabetes·Larbi DridiAlexey V Pshezhetsky
Jan 13, 2015·Biochemical and Biophysical Research Communications·Judith PetersMichael Schwake
Sep 15, 2014·Matrix Biology : Journal of the International Society for Matrix Biology·Jenny K SabolJulie A Leary
Nov 14, 2015·Journal of Lipid Research·Taroh Kinoshita, Morihisa Fujita
Sep 16, 2014·PloS One·Victoria SmutovaAlexey V Pshezhetsky
Aug 20, 2014·The Journal of Biological Chemistry·Björn KowalewskiMarkus Damme
May 16, 2017·Oncotarget·Thuy Linh NguyenBernd Schröder
Feb 8, 2013·Traffic·Michael SchwakePaul Saftig
Oct 18, 2020·The FEBS Journal·Sönke Rudnik, Markus Damme
Oct 28, 2020·International Journal of Molecular Sciences·Noelia BenetóIsaac Canals
Sep 5, 2021·Proceedings of the National Academy of Sciences of the United States of America·Carys S JonesAnthony J Clarke

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.