ER-Golgi dynamics of HS-modifying enzymes via vesicular trafficking is a critical prerequisite for the delineation of HS biosynthesis

Carbohydr Polym. 2021 Mar 1:255:117477. doi: 10.1016/j.carbpol.2020.117477. Epub 2020 Dec 3.

Abstract

The cell surface and extracellular matrix polysaccharide, heparan sulfate (HS) conveys chemical information to control crucial biological processes. HS chains are synthesized in a non-template driven process mainly in the Golgi apparatus, involving a large number of enzymes capable of subtly modifying its substitution pattern, hence, its interactions and biological effects. Changes in the localization of HS-modifying enzymes throughout the Golgi were found to correlate with changes in the structure of HS, rather than protein expression levels. Following BFA treatment, the HS-modifying enzymes localized preferentially in COPII vesicles and at the trans-Golgi. Shortly after heparin treatment, the HS-modifying enzyme moved from cis to trans-Golgi, which coincided with increased HS sulfation. Finally, it was shown that COPI subunits and Sec24 gene expression changed. Collectively, these findings demonstrate that knowledge of the ER-Golgi dynamics of HS-modifying enzymes via vesicular trafficking is a critical prerequisite for the complete delineation of HS biosynthesis.

Keywords: Biosynthesis; COPI; COPII; Golgi apparatus; Heparan sulfate.

MeSH terms

  • Biological Transport / drug effects
  • Brefeldin A / pharmacology
  • COP-Coated Vesicles / enzymology*
  • COP-Coated Vesicles / genetics
  • Cell Membrane / chemistry
  • Cell Membrane / drug effects
  • Cell Membrane / enzymology
  • Endoplasmic Reticulum / chemistry
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / enzymology*
  • Gene Expression Regulation
  • Golgi Apparatus / chemistry
  • Golgi Apparatus / drug effects
  • Golgi Apparatus / enzymology*
  • Heparin / pharmacology
  • Heparitin Sulfate / biosynthesis*
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / enzymology
  • Humans
  • Plasmids / chemistry
  • Plasmids / metabolism
  • Primary Cell Culture
  • Transfection
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism

Substances

  • SEC24A protein, human
  • Vesicular Transport Proteins
  • Brefeldin A
  • Heparin
  • Heparitin Sulfate