TECPR2: a new autophagy link for neurodegeneration

Autophagy. 2013 May;9(5):801-2. doi: 10.4161/auto.23961. Epub 2013 Feb 25.

Abstract

Autophagy dysfunction has been implicated in a group of progressive neurodegenerative diseases, and has been reported to play a major role in the pathogenesis of these disorders. We have recently reported a recessive mutation in TECPR2, an autophagy-implicated WD repeat-containing protein, in five individuals with a novel form of monogenic hereditary spastic paraparesis (HSP). We found that diseased skin fibroblasts had a decreased accumulation of the autophagy-initiation protein MAP1LC3B/LC3B, and an attenuated delivery of both LC3B and the cargo-recruiting protein SQSTM1/p62 to the lysosome where they are subject to degradation. The discovered TECPR2 mutation reveals for the first time a role for aberrant autophagy in a major class of Mendelian neurodegenerative diseases, and suggests mechanisms by which impaired autophagy may impinge on a broader scope of neurodegeneration.

Keywords: MAP1LC3; autophagy; endosomal trafficking; exome sequencing; hereditary spastic paraparesis; skin fibroblasts.

MeSH terms

  • Autophagy*
  • HeLa Cells
  • Humans
  • Mitochondria / metabolism
  • Mutation / genetics
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / pathology*
  • Paraparesis, Spastic / genetics
  • Paraparesis, Spastic / pathology
  • Proteolysis
  • Signal Transduction

Substances

  • Nerve Tissue Proteins