Roles of glycosaminoglycans as regulators of ligand/receptor complexes

Open Biol. 2018 Oct 3;8(10):180026. doi: 10.1098/rsob.180026.

Abstract

Glycosaminoglycans (GAGs) play a widespread role in embryonic development, as deletion of enzymes that contribute to GAG synthesis lead to deficiencies in cell migration and tissue modelling. Despite the biochemical and structural characterization of individual protein/GAG interactions, there is no concept available that links the molecular mechanisms of GAG/protein engagements to tissue development. Here, we focus on the role of GAG polymers in mediating interactions between cell surface receptors and their ligands. We categorize several switches that lead to ligand activation, inhibition, selection and addition, based on recent structural studies of select receptor/ligand complexes. Based on these principles, we propose that individual GAG polymers may affect several receptor pathways in parallel, orchestrating a cellular response to an environmental cue. We believe that it is worthwhile to study the role of GAGs as molecular switches, as this may lead to novel drug candidates to target processes such as angiogenesis, neuroregeneration and tumour metastasis.

Keywords: circuit modifiers; drug targets; extracellular matrix; glycosaminoglycans; protein/protein interactions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Extracellular Matrix / metabolism
  • Glycosaminoglycans / chemistry*
  • Glycosaminoglycans / metabolism*
  • Hedgehog Proteins / chemistry
  • Hedgehog Proteins / metabolism
  • Humans
  • Ligands
  • Mammals
  • Models, Molecular
  • Molecular Conformation
  • Netrins / chemistry
  • Netrins / metabolism
  • Receptors, Cell Surface / chemistry*
  • Receptors, Cell Surface / metabolism*

Substances

  • Glycosaminoglycans
  • Hedgehog Proteins
  • Ligands
  • Netrins
  • Receptors, Cell Surface