Schwann cell-derived neuregulin-2alpha can function as a cell-attached activator of muscle acetylcholine receptor expression.
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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.
author list (cited authors)
Ponomareva, O. N., Fischer, T. M., Lai, C., & Rimer, M.
complete list of authors
Ponomareva, Olga N||Fischer, Tobias M||Lai, Cary||Rimer, Mendell