Snapin deficiency is associated with developmental defects of the central nervous system

Bing Zhou, Yi Bing Zhu, Lin Lin, Qian Cai, Zu Hang Sheng

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


The autophagy-lysosomal pathway is an intracellular degradation process essential for maintaining neuronal homoeostasis. Defects in this pathway have been directly linked to a growing number of neurodegenerative disorders. We recently revealed that Snapin plays a critical role in co-ordinating dynein-driven retrograde transport and late endosomal-lysosomal trafficking, thus maintaining efficient autophagy-lysosomal function. Deleting snapin in neurons impairs lysosomal proteolysis and reduces the clearance of autolysosomes. The role of the autophagy-lysosomal system in neuronal development is, however, largely uncharacterized. Here, we report that snapin deficiency leads to developmental defects in the central nervous system. Embryonic snapin-/- mouse brain showed reduced cortical plates and intermediate zone cell density, increased apoptotic death in the cortex and third ventricle, enhanced membrane-bound LC3-II staining associated with autophagic vacuoles and an accumulation of polyubiquitinated proteins in the cortex and hippocampus. Thus our results provide in vivo evidence for the essential role of late endocytic transport and autophagy-lysosomal function in maintaining neuronal survival and development of the mammalian central nervous system. In addition, our study supports the existence of a functional interplay between the autophagy-lysosome and ubiquitin-proteasome systems in the protein quality-control process.

Original languageEnglish (US)
Pages (from-to)151-158
Number of pages8
JournalBioscience Reports
Issue number2
StatePublished - Apr 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


  • Apoptotic cell death
  • Autophagy
  • Late endocytic trafficking
  • Lysosome
  • Neuronal development
  • Ubiquitin


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