Schwann cell-derived neuregulin-2alpha can function as a cell-attached activator of muscle acetylcholine receptor expression.
Here we show that neuregulin-2 (Nrg-2) alpha- and beta-isoforms can activate acetylcholine receptor (AChR) transcription as surface-attached ligands. More importantly, we demonstrate that Schwann cells that express Nrg-2alpha on their cell surface, the same Nrg-2 isoform expressed by terminal Schwann cells at the neuromuscular junction, can induce AChR expression if brought into cell-to-cell contact with myotubes specifically expressing ErbB4. These Schwann cells, the D6P2T cell line, induce AChR expression apparently as well as 293T cells transfected with Nrg-2beta, the isoform with the highest AChR-inducing activity when presented in a soluble form. These results provide a potential role for the previously reported, paradoxical perisynaptic accumulation of Nrg-2alpha, the isoform with the least AChR-inducing activity when presented in a soluble form. They also raise the possibility that Schwann cell-derived Nrg-2 could activate ErbB receptors on the synaptic sarcolemma and that this could account, at least in part, for the Nrg-mediated regulation of AChR expression.
Ponomareva
Olga N
ON
Section of Neurobiology, University of Texas, Austin, Texas, USA.
Fischer
Tobias M
TM
Lai
Cary
C
Rimer
Mendell
M
D000818:Animals; D000831:Animals, Newborn; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000294:innervation* / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D066247:Receptor, ErbB-4; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*
D008565:Membrane Proteins; D009414:Nerve Growth Factors; C491452:Nrg2 protein, rat; D020033:Protein Isoforms; D011978:Receptors, Nicotinic; D066246:ErbB Receptors; C587691:Erbb4 protein, rat; D066247:Receptor, ErbB-4