gamma-AChR/epsilon-AChR switch at agrin-induced postsynaptic-like apparatus in skeletal muscle |
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Authors: | M Rimer I Mathiesen T L?mo UJ McMahan |
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Affiliation: | Department of Neurobiology, Stanford University School of Medicine, California 94305, USA. |
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Abstract: | We transfected the extrajunctional region of denervated soleus muscles in adult rats with neural agrin cDNA to induce myofibers to form postsynaptic-like apparatus containing acetylcholine receptor (AChR) aggregates. By 1 week approximately 30% of the AChR aggregates contained a mixture of epsilon-AChRs and gamma-AChRs while approximately 70% had only gamma-AChRs. If the transfected muscles were reinnervated in the original junctional region, the postsynaptic-like apparatus, despite the absence of apposed axon terminals, gradually came to have only epsilon-AChRs. We conclude that at the postsynaptic apparatus of ectopic neuromuscular junctions formed by a foreign nerve implanted into the extra-junctional region of denervated muscles, agrin secreted by the axon terminal plays a direct role in the gamma-AChR/epsilon-AChR switch that occurs as the apparatus reaches maturity. Our findings, together with results from other studies, indicate further that agrin and acetylcholine are the only nerve-derived factors required for this switch. |
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