Science (American Association for the Advancement of Science), 2009-01, Vol.323 (5910), p.124-127
2009
Details
- Autor(en) / Beteiligte
- Titel
- Regulation of Neuronal Survival Factor MEF2D by Chaperone-Mediated Autophagy
- Ist Teil von
- Science (American Association for the Advancement of Science), 2009-01, Vol.323 (5910), p.124-127
- Ort / Verlag
- United States: American Association for the Advancement of Science
- Erscheinungsjahr
- 2009
- Link zum Volltext
- Quelle
- American Association for the Advancement of Science
- Beschreibungen/Notizen
- Chaperone-mediated autophagy controls the degradation of selective cytosolic proteins and may protect neurons against degeneration. In a neuronal cell line, we found that chaperone-mediated autophagy regulated the activity of myocyte enhancer factor 2D (MEF2D), a transcription factor required for neuronal survival. MEF2D was observed to continuously shuttle to the cytoplasm, interact with the chaperone Hsc70, and undergo degradation. Inhibition of chaperone-mediated autophagy caused accumulation of inactive MEF2D in the cytoplasm. MEF2D levels were increased in the brains of α-synuclein transgenic mice and patients with Parkinson's disease. Wild-type α-synuclein and a Parkinson's disease-associated mutant disrupted the MEF2D-Hsc70 binding and led to neuronal death. Thus, chaperone-mediated autophagy modulates the neuronal survival machinery, and dysregulation of this pathway is associated with Parkinson's disease.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0036-8075eISSN: 1095-9203DOI: 10.1126/science.1166088Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2666000
- Format
- –
- Schlagworte
- Actins, alpha-Synuclein - genetics, alpha-Synuclein - metabolism, Amino Acid Motifs, Ammonium Chloride - pharmacology, Animals, Autophagy, Brain - metabolism, Cell Line, Cell Nucleus - metabolism, Cell Survival, Cellular biology, Cytoplasm, Cytoplasm - metabolism, Delta cells, DNA, DNA - metabolism, Gene expression regulation, HEK293 cells, HSC70 Heat-Shock Proteins - metabolism, Lysosomal-Associated Membrane Protein 2 - metabolism, Lysosomes, Lysosomes - metabolism, MADS Domain Proteins - metabolism, MEF2 Transcription Factors, Mice, Mice, Transgenic, Molecular Chaperones - metabolism, Mutation, Myogenic Regulatory Factors - chemistry, Myogenic Regulatory Factors - metabolism, Neurology, Neurons, Neurons - cytology, Neurons - metabolism, Parkinson Disease - metabolism, Pharmacology, Plasmids, Protein Binding, Protein Transport, Proteins, Rats, Rats, Long-Evans