Document Detail

Snapin deficiency is associated with developmental defects of the central nervous system.
MedLine Citation:
PMID:  20946101     Owner:  NLM     Status:  In-Process    
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.
Bing Zhou; Yi-Bing Zhu; Lin Lin; Qian Cai; Zu-Hang Sheng
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural    
Journal Detail:
Title:  Bioscience reports     Volume:  31     ISSN:  1573-4935     ISO Abbreviation:  Biosci. Rep.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2010-11-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8102797     Medline TA:  Biosci Rep     Country:  United States    
Other Details:
Languages:  eng     Pagination:  151-8     Citation Subset:  IM    
Synaptic Function Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892-3706, USA.
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