Modulation of nicotinic acetylcholine receptor turnover by tyrosine phosphorylation in rat myotubes.
The muscle nicotinic acetylcholine receptor (AChR) turns over at different rates depending on stage of synaptogenesis and innervation. Tyrosine phosphorylation modulates desensitization, interaction with cytoskeleton and lateral mobility in the membrane of AChR. To determine whether tyrosine phosphorylation also modulates the turnover of AChR, myotubes in vitro were exposed to the tyrosine phosphatase inhibitor pervanadate. Our data indicate that a transient increase of phosphotyrosine levels stabilized a fraction of AChRs. The effects were limited to the non-epsilon subunit-containing AChRs already present in the membrane. Tyrosine phosphorylation of the receptor occurred on the beta subunit, was transient and stable molecules were not selectively tyrosine phosphorylated. The data indicate that modulation of phosphotyrosine levels in muscle cells provides signals to control AChR metabolic stability.
Sava
A
A
Department of Medicine & Public Health, Section of Pharmacology, School of Medicine, University of Verona, Policlinico Borgo Roma, 37134 Verona, Italy.
Barisone
I
I
Di Mauro
D
D
Fumagalli
G
G
Sala
C
C
D000818:Animals; D019921:Biotinylation; D002038:Bungarotoxins / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007457:Iodine Radioisotopes; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*; D014638:Vanadates / Q000494:pharmacology
D002038:Bungarotoxins; D004791:Enzyme Inhibitors; D007457:Iodine Radioisotopes; D011978:Receptors, Nicotinic; C076715:pervanadate; D019000:Phosphotyrosine; D014638:Vanadates; D014443:Tyrosine; D017027:Protein Tyrosine Phosphatases