Neuregulin-1beta induces neurite extension and arborization in cultured hippocampal neurons

Mol Cell Neurosci. 2004 Dec;27(4):379-93. doi: 10.1016/j.mcn.2004.08.001.

Abstract

Neuregulin-1 (NRG-1) growth and differentiation factors and their erbB receptors are hypothesized to promote embryonic hippocampal neuron differentiation via as yet unknown mechanisms. We have found that NRG-1beta increases the outgrowth of primary neurites, neuronal area, total neurite length, and neuritic branching in E18 hippocampal neurons. NRG-1beta effects on neurite extension and arborization are similar to, but not additive with, those of brain-derived neurotrophic factor and reflect direct NRG-1 action on hippocampal neurons as these cells express the NRG-1 receptors erbB2 and erbB4, the erbB-specific inhibitor PD158780 decreases NRG-1beta induced neurite outgrowth, and NRG-1beta stimulation induces p42/44 ERK phosphorylation. Pharmacological inhibition of p42/44 ERK and protein kinase C (PKC), but not PI3K or p38 MAP kinase, inhibits NRG-1beta-induced neurite extension and elaboration. We conclude that NRG-1beta stimulates hippocampal neurite extension and arborization via a signaling pathway that involves erbB membrane tyrosine kinases (erbB2 and/or erbB4), p42/44 ERK, and PKC.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism
  • Brain-Derived Neurotrophic Factor / pharmacology
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Cells, Cultured
  • Enzyme Inhibitors / pharmacology
  • ErbB Receptors / metabolism
  • Hippocampus / cytology
  • Hippocampus / embryology*
  • Hippocampus / metabolism
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Nerve Tissue Proteins / pharmacology
  • Nerve Tissue Proteins / physiology*
  • Neuregulin-1
  • Neurites / drug effects
  • Neurites / metabolism*
  • Neurites / ultrastructure
  • Protein Isoforms / pharmacology
  • Protein Isoforms / physiology
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism
  • Rats
  • Receptor, ErbB-2 / metabolism
  • Receptor, ErbB-4
  • Signal Transduction / physiology

Substances

  • Brain-Derived Neurotrophic Factor
  • Enzyme Inhibitors
  • Nerve Tissue Proteins
  • Neuregulin-1
  • Nrg1 protein, rat
  • Protein Isoforms
  • ErbB Receptors
  • Erbb4 protein, rat
  • Receptor, ErbB-2
  • Receptor, ErbB-4
  • Protein Kinase C
  • Mitogen-Activated Protein Kinase 1