Regulation of neuronal survival factor MEF2D by chaperone-mediated autophagy.
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 alpha-synuclein transgenic mice and patients with Parkinson's disease. Wild-type alpha-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.
Mesh Terms:
Amino Acid Motifs, Ammonium Chloride, Animals, Autophagy, Brain, Cell Line, Cell Nucleus, Cell Survival, Cytoplasm, DNA, HSC70 Heat-Shock Proteins, Lysosomal-Associated Membrane Protein 2, Lysosomes, MADS Domain Proteins, MEF2 Transcription Factors, Mice, Mice, Transgenic, Molecular Chaperones, Myogenic Regulatory Factors, Neurons, Parkinson Disease, Protein Binding, Protein Transport, Rats, Rats, Long-Evans, alpha-Synuclein
Amino Acid Motifs, Ammonium Chloride, Animals, Autophagy, Brain, Cell Line, Cell Nucleus, Cell Survival, Cytoplasm, DNA, HSC70 Heat-Shock Proteins, Lysosomal-Associated Membrane Protein 2, Lysosomes, MADS Domain Proteins, MEF2 Transcription Factors, Mice, Mice, Transgenic, Molecular Chaperones, Myogenic Regulatory Factors, Neurons, Parkinson Disease, Protein Binding, Protein Transport, Rats, Rats, Long-Evans, alpha-Synuclein
Science
Date: Jan. 02, 2009
PubMed ID: 19119233
View in: Pubmed Google Scholar
Download Curated Data For This Publication
226467
Switch View:
- Interactions 3