Neuregulin-2 is synthesized by motor neurons and terminal Schwann cells and activates acetylcholine receptor transcription in muscle cells expressing ErbB4

Mol Cell Neurosci. 2004 Jun;26(2):271-81. doi: 10.1016/j.mcn.2004.02.002.

Abstract

Acetylcholine receptor (AChR) genes are transcribed selectively in synaptic nuclei of skeletal muscle fibers, leading to accumulation of the mRNAs encoding AChR subunits at synaptic sites. The signals that regulate synapse-specific transcription remain elusive, though Neuregulin-1 is considered a favored candidate. Here, we show that motor neurons and terminal Schwann cells express neuregulin-2, a neuregulin-1-related gene. In skeletal muscle, Neuregulin-2 protein is concentrated at synaptic sites, where it accumulates adjacent to terminal Schwann cells. Neuregulin-2 stimulates AChR transcription in cultured myotubes expressing ErbB4, as well as ErbB3 and ErbB2, but not in myotubes expressing only ErbB3 and ErbB2. Thus, Neuregulin-2 is a candidate for a signal that regulates synaptic differentiation.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cells, Cultured
  • Choline O-Acetyltransferase / metabolism
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Gene Expression Regulation, Developmental / genetics
  • Glycoproteins / genetics
  • Glycoproteins / metabolism
  • Motor Neurons / cytology
  • Motor Neurons / metabolism*
  • Muscle Fibers, Skeletal / cytology
  • Muscle Fibers, Skeletal / metabolism
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / innervation
  • Muscle, Skeletal / metabolism*
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / metabolism*
  • Neuromuscular Junction / cytology
  • Neuromuscular Junction / metabolism
  • Phosphorylation
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Receptor, ErbB-2
  • Receptor, ErbB-3 / genetics
  • Receptor, ErbB-3 / metabolism
  • Receptor, ErbB-4
  • Receptors, Cholinergic / genetics
  • Receptors, Cholinergic / metabolism*
  • Schwann Cells / cytology
  • Schwann Cells / metabolism*
  • Synaptic Membranes / genetics
  • Synaptic Membranes / metabolism
  • Transcriptional Activation / genetics

Substances

  • Glycoproteins
  • Nerve Growth Factors
  • Nrg2 protein, rat
  • Receptors, Cholinergic
  • Choline O-Acetyltransferase
  • Egfr protein, rat
  • ErbB Receptors
  • Erbb2 protein, rat
  • Erbb4 protein, rat
  • Receptor, ErbB-2
  • Receptor, ErbB-3
  • Receptor, ErbB-4