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
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetylcholine / pharmacology
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Alternative Splicing / physiology
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Amino Acid Sequence
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Animals
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Antineoplastic Agents / chemistry*
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Antineoplastic Agents / metabolism
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Axons / chemistry
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Axons / physiology
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Chick Embryo
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Culture Media, Conditioned
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Cysteine / analysis*
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DNA, Complementary
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Gene Expression Regulation, Developmental*
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Glycoproteins / chemistry*
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Glycoproteins / genetics
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Isomerism
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Molecular Sequence Data
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Motor Neurons / chemistry
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Motor Neurons / drug effects
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Motor Neurons / ultrastructure
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Nerve Growth Factors / chemistry
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Nerve Growth Factors / genetics
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Neuregulins
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Phosphorylation
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Presynaptic Terminals / physiology
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Receptors, Nicotinic / genetics*
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Recombinant Proteins / metabolism
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Spinal Cord / cytology
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Spinal Cord / embryology
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Sympathetic Nervous System / chemistry
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Sympathetic Nervous System / cytology
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Sympathetic Nervous System / embryology
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Tyrosine / metabolism
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Up-Regulation / genetics
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Viscera / innervation
Substances
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Antineoplastic Agents
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Culture Media, Conditioned
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DNA, Complementary
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Glycoproteins
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Nerve Growth Factors
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Neuregulins
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Receptors, Nicotinic
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Recombinant Proteins
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Tyrosine
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Cysteine
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Acetylcholine
Associated data
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GENBANK/AF045654
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GENBANK/AF045655
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GENBANK/AF045656