gamma-AChR/epsilon-AChR switch at agrin-induced postsynaptic-like apparatus in skeletal muscle.
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.
Rimer
M
M
Department of Neurobiology, Stanford University School of Medicine, California 94305, USA.
Mathiesen
I
I
Lømo
T
T
McMahan
U J
UJ
D018171:Agrin / Q000494:pharmacology*; D000818:Animals; D007536:Isomerism; D008297:Male; D009121:Muscle Denervation; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000294:innervation*; D009469:Neuromuscular Junction / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011950:Receptors, Cholinergic / Q000378:metabolism*; D013569:Synapses / Q000502:physiology*
D018171:Agrin; D011950:Receptors, Cholinergic