A cysteine-rich isoform of neuregulin controls the level of expression of neuronal nicotinic receptor channels during synaptogenesis.
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.
Yang
X
X
The Center for Neurobiology and Behavior and the Department of Anatomy and Cell Biology, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA.
Kuo
Y
Y
Devay
P
P
Yu
C
C
Role
L
L
D000109:Acetylcholine / Q000494:pharmacology; D017398:Alternative Splicing / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism; D001369:Axons / Q000737:chemistry / Q000502:physiology; D002642:Chick Embryo; D017077:Culture Media, Conditioned; D003545:Cysteine / Q000032:analysis*; D018076:DNA, Complementary; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000737:chemistry* / Q000235:genetics; D007536:Isomerism; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000737:chemistry / Q000187:drug effects / Q000648:ultrastructure; D009414:Nerve Growth Factors / Q000737:chemistry / Q000235:genetics; D020880:Neuregulins; D010766:Phosphorylation; D017729:Presynaptic Terminals / Q000502:physiology; D011978:Receptors, Nicotinic / Q000235:genetics*; D011994:Recombinant Proteins / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology; D013564:Sympathetic Nervous System / Q000737:chemistry / Q000166:cytology / Q000196:embryology; D014443:Tyrosine / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D014781:Viscera / Q000294:innervation
D000970:Antineoplastic Agents; D017077:Culture Media, Conditioned; D018076:DNA, Complementary; D006023:Glycoproteins; D009414:Nerve Growth Factors; D020880:Neuregulins; D011978:Receptors, Nicotinic; D011994:Recombinant Proteins; D014443:Tyrosine; D003545:Cysteine; D000109:Acetylcholine