期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 114, 期 2, 页码 346-351出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1608576114
关键词
GM130; Golgi apparatus; polarized secretion; Purkinje cell; ataxia
资金
- National Natural Sciences Foundation of China [31571379, 31371378]
- Biotechnology and Biological Sciences Research Council [BB/I007717/1, BB/H531600/1]
- BBSRC [BB/I007717/1, BB/H531600/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/H531600/1, BB/I007717/1] Funding Source: researchfish
The Golgi apparatus lies at the heart of the secretory pathway where it is required for secretory trafficking and cargo modification. Disruption of Golgi architecture and function has been widely observed in neurodegenerative disease, but whether Golgi dysfunction is causal with regard to the neurodegenerative process, or is simply a manifestation of neuronal death, remains unclear. Here we report that targeted loss of the golgin GM130 leads to a profound neurological phenotype in mice. Global KO of mouse GM130 results in developmental delay, severe ataxia, and postnatal death. We further show that selective deletion of GM130 in neurons causes fragmentation and defective positioning of the Golgi apparatus, impaired secretory trafficking, and dendritic atrophy in Purkinje cells. These cellular defects manifest as reduced cerebellar size and Purkinje cell number, leading to ataxia. Purkinje cell loss and ataxia first appear during postnatal development but progressively worsen with age. Our data therefore indicate that targeted disruption of the mammalian Golgi apparatus and secretory traffic results in neuronal degeneration in vivo, supporting the view that Golgi dysfunction can play a causative role in neurodegeneration.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据