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.
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Research Article|
November 23 2010
Snapin deficiency is associated with developmental defects of the central nervous system
Bing Zhou;
Bing Zhou
1
*Synaptic Function Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892-3706, U.S.A.
†Department of Neurobiology, Shanghai Jiao-Tong University School of Medicine, Shanghai, People's Republic of China
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Yi-Bing Zhu;
Yi-Bing Zhu
1
*Synaptic Function Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892-3706, U.S.A.
†Department of Neurobiology, Shanghai Jiao-Tong University School of Medicine, Shanghai, People's Republic of China
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Lin Lin;
Lin Lin
1
†Department of Neurobiology, Shanghai Jiao-Tong University School of Medicine, Shanghai, People's Republic of China
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Qian Cai;
Qian Cai
*Synaptic Function Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892-3706, U.S.A.
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Zu-Hang Sheng
Zu-Hang Sheng
2
*Synaptic Function Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892-3706, U.S.A.
2To whom correspondence should be addressed (email shengz@ninds.nih.gov).
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Publisher: Portland Press Ltd
Received:
October 07 2010
Accepted:
October 14 2010
Accepted Manuscript online:
October 14 2010
Online ISSN: 1573-4935
Print ISSN: 0144-8463
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biosci Rep (2011) 31 (2): 151–158.
Article history
Received:
October 07 2010
Accepted:
October 14 2010
Accepted Manuscript online:
October 14 2010
Citation
Bing Zhou, Yi-Bing Zhu, Lin Lin, Qian Cai, Zu-Hang Sheng; Snapin deficiency is associated with developmental defects of the central nervous system. Biosci Rep 1 April 2011; 31 (2): 151–158. doi: https://doi.org/10.1042/BSR20100110
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