Regulation of neuronal survival factor MEF2D by chaperone-mediated autophagy.

Academic Article

Abstract

  • 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.
  • Authors

    Published In

  • Science  Journal
  • Keywords

  • 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
  • Digital Object Identifier (doi)

    Author List

  • Yang Q; She H; Gearing M; Colla E; Lee M; Shacka JJ; Mao Z
  • Start Page

  • 124
  • End Page

  • 127
  • Volume

  • 323
  • Issue

  • 5910