期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 24, 页码 -出版社
MDPI
DOI: 10.3390/ijms232415742
关键词
ataxia; motor neuron; neurofilament; intermediate filaments; chaperone; J domain; vimentin
Autosomal Recessive Spastic Ataxia of the Charlevoix Saguenay (ARSACS) is a genetic disease caused by mutation in the SACS gene, resulting in loss of function of the protein sacsin. The SacsJ domain of sacsin plays a key role in regulating the neurofilament (NF) and vimentin intermediate filament (IF) networks in cells.
Autosomal Recessive Spastic Ataxia of the Charlevoix Saguenay (ARSACS) is caused by mutation in the SACS gene resulting in loss of function of the protein sacsin. A key feature is the formation of abnormal bundles of neurofilaments (NF) in neurons and vimentin intermediate filaments (IF) in cultured fibroblasts, suggesting a role of sacsin in IF homeostasis. Sacsin contains a J domain (SacsJ) homologous to Hsp40, that can interact with Hsp70 chaperones. The SacsJ domain resolved NF bundles in cultured Sacs(-/-) neurons. Having studied the mechanism using NF assembled in vitro from purified NF proteins, we report that the SacsJ domain interacts with NF proteins to disassemble NFL filaments, and to inhibit their initial assembly. A cell-penetrating peptide derived from this domain, SacsJ-myc-TAT was efficient in disassembling NF bundles in cultured Sacs(-/-) motor neurons, restoring the NF network; however, there was some loss of vimentin IF and NF in cultured Sacs(+/+) fibroblasts and motor neurons, respectively. These results suggest that sacsin through its SacsJ domain is a key regulator of NF and vimentin IF networks in cells.
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