Protein synthesis is required for the denervation-triggered activation of acetylcholine receptor genes.
The effect of cycloheximide (CHX) on denervation-induced acetylcholine receptor (AChR) expression was investigated in chickens one day after nerve section, using probe excess solution hybridization to quantitate AChR alpha-subunit gene transcript levels and run-on analysis to measure subunit gene activity. The increase in alpha-subunit transcripts that normally follows denervation was prevented when drug treatment was commenced 2 h before or after denervation but was not blocked when CHX administration was begun 6 h after the operation. Drug-induced reduction of transcript levels results from decreased activity of genes coding for the alpha-, delta-, and gamma-subunits; in contrast, the transcription rates of several non-receptor genes are not affected by CHX. The results suggest that the de novo synthesis of a transcriptional activator is required as a mediating event in the signalling pathway linking the plasma membrane and AChR gene expression.
Tsay
H J
HJ
Department of Biochemistry and Cell Biology, State University of New York, Stony Brook 11794.
Neville
C M
CM
Schmidt
J
J
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002645:Chickens; D003513:Cycloheximide / Q000494:pharmacology; D015342:DNA Probes; D003609:Dactinomycin / Q000494:pharmacology; D003714:Denervation; D005786:Gene Expression Regulation; D046911:Macromolecular Substances; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011950:Receptors, Cholinergic / Q000235:genetics*; D012584:Sciatic Nerve / Q000502:physiology*
D015342:DNA Probes; D046911:Macromolecular Substances; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D003609:Dactinomycin; D003513:Cycloheximide