Strychnine-blocked glycine receptor is removed from synapses by a shift in insertion/degradation equilibrium.
The long-term inhibition by strychnine of glycine receptor activity in neurons provokes the receptor's selective intracellular accumulation and disappearance from synapses. This could result either from a disruption of the postsynaptic anchoring of the receptor or from an arrest of its exocytic transport. In this study we combined biochemical and fluorescence microscopy analyses to determine on a short time scale the fate of the strychnine-inactivated glycine receptor. Quantification of the cellular content of receptor showed that the rapid accumulation depends on protein synthesis. Cell surface biotinylation of neurons demonstrated that strychnine did not accelerate the turnover rate of the receptor. Labeling of endosomes indicated that, in strychnine-treated cells, the accumulated receptor is not blocked in the endosomal transport pathway. Taken together, these results indicate that strychnine does not destabilize the postsynaptic receptor but triggers its disappearance from synapses by a nondegradative sequestration of newly synthesized molecules in a nonendocytic compartment.
Rasmussen
Hanne
H
Laboratoire de Biologie Cellulaire de la Synapse Normale et Pathologique, INSERM U497, Ecole Normale Supérieure, Paris, France.
Rasmussen
Trine
T
Triller
Antoine
A
Vannier
Christian
C
D000818:Animals; D000870:Anterior Horn Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001710:Biotin / Q000494:pharmacology; D019921:Biotinylation; D002451:Cell Compartmentation / Q000187:drug effects / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism; D005333:Fetus; D018684:Glycine Agents / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018009:Receptors, Glycine / Q000187:drug effects / Q000378:metabolism*; D013331:Strychnine / Q000494:pharmacology*; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D018684:Glycine Agents; D011500:Protein Synthesis Inhibitors; D018009:Receptors, Glycine; D001710:Biotin; D003513:Cycloheximide; D013331:Strychnine