Neuron (Cambridge, Mass.), 2012-04, Vol.74 (2), p.277-284
2012
Details
- Autor(en) / Beteiligte
- Titel
- Regulation of Presynaptic Neurotransmission by Macroautophagy
- Ist Teil von
- Neuron (Cambridge, Mass.), 2012-04, Vol.74 (2), p.277-284
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2012
- Link zum Volltext
- Quelle
- EZB-FREE-00999 freely available EZB journals
- Beschreibungen/Notizen
- mTOR is a regulator of cell growth and survival, protein synthesis-dependent synaptic plasticity, and autophagic degradation of cellular components. When triggered by mTOR inactivation, macroautophagy degrades long-lived proteins and organelles via sequestration into autophagic vacuoles. mTOR further regulates synaptic plasticity, and neurodegeneration occurs when macroautophagy is deficient. It is nevertheless unknown whether macroautophagy modulates presynaptic function. We find that the mTOR inhibitor rapamycin induces formation of autophagic vacuoles in prejunctional dopaminergic axons with associated decreased axonal profile volumes, synaptic vesicle numbers, and evoked dopamine release. Evoked dopamine secretion was enhanced and recovery was accelerated in transgenic mice in which macroautophagy deficiency was restricted to dopaminergic neurons; rapamycin failed to decrease evoked dopamine release in the striatum of these mice. Macroautophagy that follows mTOR inhibition in presynaptic terminals, therefore, rapidly alters presynaptic structure and neurotransmission. ► Macroautophagy can rapidly inhibit neurotransmitter release ► mTOR inhibition rapidly elicits local presynaptic macroautophagy ► Local presynaptic autophagy appears to degrade synaptic vesicles ► Chronic autophagy deficiency increases transmitter release and axon size When triggered by mTOR inactivation, macroautophagy degrades proteins and organelles via sequestration into autophagic vacuoles. Hernandez et al. demonstrate a role in presynaptic terminals for macroautophagy that follows mTOR inhibition in the rapid alteration of presynaptic structure and neurotransmission.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0896-6273eISSN: 1097-4199DOI: 10.1016/j.neuron.2012.02.020Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3578406
- Format
- –
- Schlagworte
- 8-Hydroxy-2-(di-n-propylamino)tetralin - analogs & derivatives, 8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology, Analysis of Variance, Animals, Autophagy, Autophagy - drug effects, Autophagy - genetics, Autophagy-Related Protein 7, Behavior, Behavior, Animal - drug effects, Brain - cytology, Brain - metabolism, Corpus Striatum - drug effects, Dopamine, Dopamine - metabolism, Dopamine Plasma Membrane Transport Proteins - genetics, Dopamine Plasma Membrane Transport Proteins - metabolism, Electrochemistry, Gene Expression Regulation - drug effects, Gene Expression Regulation - genetics, Genotype, Immunosuppressive Agents - pharmacology, In Vitro Techniques, Male, Mice, Mice, Transgenic, Microscopy, Electron, Transmission, Microtubule-Associated Proteins - genetics, Microtubule-Associated Proteins - metabolism, Neurons, Parkinson's disease, Presynaptic Terminals - metabolism, Presynaptic Terminals - ultrastructure, Protein synthesis, Proteins, RNA, Messenger - genetics, Rodents, Sirolimus - pharmacology, TOR Serine-Threonine Kinases - antagonists & inhibitors, TOR Serine-Threonine Kinases - metabolism, Tyrosine 3-Monooxygenase - metabolism