A cysteine-rich isoform of neuregulin controls the level of expression of neuronal nicotinic receptor channels during synaptogenesis

Neuron. 1998 Feb;20(2):255-70. doi: 10.1016/s0896-6273(00)80454-7.

Abstract

We report here that neuregulin (NRG) isoforms with a conserved cysteine-rich domain (CRD) in their N terminus regulate expression of nicotinic acetylcholine receptors (nAChRs) at developing interneuronal synapses and report the isolation of transmembrane NRG isoforms with this CRD within the N-terminal portion. CRD-NRG mRNA and immunoreactive protein are detected early in developing presynaptic (visceral motor) neurons. The levels of expression of CRD-NRG peak prior to the formation of synapses with their postsynaptic partners, the ganglionic sympathetic neurons. Recombinant CRD-NRG mimics the effects of presynaptic input on target neurons. Functional deletion of CRD-NRG from presynaptic neurons abolishes the upregulation of nAChR expression induced by input-derived soluble material. Thus, CRD-NRG appears to be both a necessary and a sufficient signal for the control of neuronal nAChR expression during synaptogenesis.

Publication types

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

MeSH terms

  • Acetylcholine / pharmacology
  • Alternative Splicing / physiology
  • Amino Acid Sequence
  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / metabolism
  • Axons / chemistry
  • Axons / physiology
  • Chick Embryo
  • Culture Media, Conditioned
  • Cysteine / analysis*
  • DNA, Complementary
  • Gene Expression Regulation, Developmental*
  • Glycoproteins / chemistry*
  • Glycoproteins / genetics
  • Isomerism
  • Molecular Sequence Data
  • Motor Neurons / chemistry
  • Motor Neurons / drug effects
  • Motor Neurons / ultrastructure
  • Nerve Growth Factors / chemistry
  • Nerve Growth Factors / genetics
  • Neuregulins
  • Phosphorylation
  • Presynaptic Terminals / physiology
  • Receptors, Nicotinic / genetics*
  • Recombinant Proteins / metabolism
  • Spinal Cord / cytology
  • Spinal Cord / embryology
  • Sympathetic Nervous System / chemistry
  • Sympathetic Nervous System / cytology
  • Sympathetic Nervous System / embryology
  • Tyrosine / metabolism
  • Up-Regulation / genetics
  • Viscera / innervation

Substances

  • Antineoplastic Agents
  • Culture Media, Conditioned
  • DNA, Complementary
  • Glycoproteins
  • Nerve Growth Factors
  • Neuregulins
  • Receptors, Nicotinic
  • Recombinant Proteins
  • Tyrosine
  • Cysteine
  • Acetylcholine

Associated data

  • GENBANK/AF045654
  • GENBANK/AF045655
  • GENBANK/AF045656