Neurotransmitters and Endothelins Acting on Radial Glial G-Protein-Coupled Receptors Are, Through Proteolytic NRG/ErbB4 Activation, Able to Modify the Migratory Behavior of Neocortical Cells and Mediate Bipolar-to-Multipolar Transition

Stem Cells Dev. 2020 Sep 1;29(17):1160-1177. doi: 10.1089/scd.2019.0133. Epub 2020 Feb 11.

Abstract

Cell-cell communication plays a central role in the guidance of migrating neurons during the development of the cerebral cortex. Neuregulins (NRGs) are essential mediators for migration and maintenance of the radial glial scaffold. We show, in this study that soluble NRG reduces neuronal motility, causes transition of bipolar cells to multipolar ones, and induces neuronal mitosis. Blocking the NRG receptor, ErbB4, results in reduction of neuron-neuron and neuron-radial glial contacts and causes an increase in neuronal motility. Blocking the radial glial metabotropic glutamate receptor 5 (mGluR5), the nonselective cation channel transient receptor potential 3 (TRPC3), or matrix metalloproteinases (MMPs) results in similar effects as ErbB4 blockade. Soluble NRG counteract the changes in motility pattern. Stimulation of other radial glial G-protein-coupled receptors (GPCRs), such as muscarinic acetylcholine receptors or endothelin receptors counteract all the effect of mGluR5 blockade, but not that of ErbB4, TRPC3, and MMP blockade. The results indicate that neurotransmitters and endothelins acting on radial glial GPCRs are, through proteolytic NRG/ErbB4 activation, able to modify the migratory behavior of neurons.

Keywords: ErbB4; TRPC; calcium; mGluR5; migration; neuregulin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Communication / drug effects
  • Cell Movement* / drug effects
  • Cell Shape / drug effects
  • Endothelins / pharmacology*
  • Mice, Inbred C57BL
  • Neocortex / cytology*
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / metabolism
  • Neuregulins / metabolism*
  • Neuroglia / drug effects
  • Neuroglia / metabolism*
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurotransmitter Agents / pharmacology*
  • Proteolysis* / drug effects
  • Receptor, ErbB-4 / metabolism*
  • Receptor, Metabotropic Glutamate 5 / metabolism
  • Receptors, G-Protein-Coupled / metabolism
  • TRPC Cation Channels / metabolism

Substances

  • Endothelins
  • Neuregulins
  • Neurotransmitter Agents
  • Receptor, Metabotropic Glutamate 5
  • Receptors, G-Protein-Coupled
  • TRPC Cation Channels
  • TRPC3 cation channel
  • Receptor, ErbB-4