Schwann cell-derived neuregulin-2α can function as a cell-attached activator of muscle acetylcholine receptor expression
✍ Scribed by Olga N. Ponomareva; Tobias M. Fischer; Cary Lai; Mendell Rimer
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- English
- Weight
- 410 KB
- Volume
- 54
- Category
- Article
- ISSN
- 0894-1491
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✦ Synopsis
Abstract
Here we show that neuregulin‐2 (Nrg‐2) α‐ and β‐isoforms can activate acetylcholine receptor (AChR) transcription as surface‐attached ligands. More importantly, we demonstrate that Schwann cells that express Nrg‐2α 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‐2β, 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‐2α, 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. © 2006 Wiley‐Liss, Inc.