Neuregulin-2 is synthesized by motor neurons and terminal Schwann cells and activates acetylcholine receptor transcription in muscle cells expressing ErbB4.
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.
Rimer
Mendell
M
Molecular Neurobiology Program, Skirball Institute of Biomolecular Medicine, NYU Medical School, New York, NY 10016, USA. rimer@mail.utexas.edu
Prieto
Anne L
AL
Weber
Janet L
JL
Colasante
Cesare
C
Ponomareva
Olga
O
Fromm
Larry
L
Schwab
Markus H
MH
Lai
Cary
C
Burden
Steven J
SJ
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000294:innervation / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3 / Q000235:genetics / Q000378:metabolism; D066247:Receptor, ErbB-4; D011950:Receptors, Cholinergic / Q000235:genetics / Q000378:metabolism*; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism*; D013570:Synaptic Membranes / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics
D002795:Choline O-Acetyltransferase; D066246:ErbB Receptors; D006023:Glycoproteins; D009414:Nerve Growth Factors; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; D011950:Receptors, Cholinergic; C491452:Nrg2 protein, rat; C483803:Egfr protein, rat; C483804:Erbb2 protein, rat; C587691:Erbb4 protein, rat