Neural agrin controls acetylcholine receptor stability in skeletal muscle fibers.
At mammalian neuromuscular junctions (NMJs), innervation induces and maintains the metabolic stability of acetylcholine receptors (AChRs). To explore whether neural agrin may cause similar receptor stabilization, we injected neural agrin cDNA of increasing transfection efficiencies into denervated adult rat soleus (SOL) muscles. As the efficiency increased, the amount of recombinant neural agrin expressed in the muscles also increased. This agrin aggregated AChRs on muscle fibers, whose half-life increased in a dose-dependent way from 1 to 10 days. Electrical muscle stimulation enhanced the stability of AChRs with short half-lives. Therefore, neural agrin can stabilize aggregated AChRs in a concentration- and activity-dependent way. However, there was no effect of stimulation on AChRs with a long half-life (10 days). Thus, at sufficiently high concentrations, neural agrin alone can stabilize AChRs to levels characteristic of innervated NMJs.
Bezakova
G
G
Department of Physiology, University of Oslo, Norway.
Rabben
I
I
Sefland
I
I
Fumagalli
G
G
Lømo
T
T
D018171:Agrin / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D003714:Denervation; D004558:Electric Stimulation; D006207:Half-Life; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009469:Neuromuscular Junction / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011950:Receptors, Cholinergic / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014162:Transfection
D018171:Agrin; D002038:Bungarotoxins; D018076:DNA, Complementary; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D011950:Receptors, Cholinergic; D011993:Recombinant Fusion Proteins