Cellular model of neuronal atrophy induced by DYNC1I1 deficiency reveals protective roles of RAS-RAF-MEK signaling.
10.1007/s13238-016-0301-6
- Author:
Zhi-Dong LIU
1
;
Su ZHANG
1
;
Jian-Jin HAO
1
;
Tao-Rong XIE
1
;
Jian-Sheng KANG
2
Author Information
1. Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200231, China.
2. Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200231, China. jskang@sibs.ac.cn.
- Publication Type:Journal Article
- Keywords:
RAS-RAF-MEK pathway;
atrophy;
autophagy;
dynein intermediate chain;
hippocampal neuron;
mitochondria
- MeSH:
Animals;
Cell Line;
Cytoplasmic Dyneins;
genetics;
metabolism;
Hippocampus;
metabolism;
pathology;
MAP Kinase Kinase Kinases;
genetics;
metabolism;
MAP Kinase Signaling System;
Mice;
Mice, Knockout;
Neurodegenerative Diseases;
genetics;
metabolism;
pathology;
Proto-Oncogene Proteins B-raf;
genetics;
metabolism;
ras Proteins;
genetics;
metabolism
- From:
Protein & Cell
2016;7(9):638-650
- CountryChina
- Language:English
-
Abstract:
Neuronal atrophy is a common pathological feature occurred in aging and neurodegenerative diseases. A variety of abnormalities including motor protein malfunction and mitochondrial dysfunction contribute to the loss of neuronal architecture; however, less is known about the intracellular signaling pathways that can protect against or delay this pathogenic process. Here, we show that the DYNC1I1 deficiency, a neuron-specific dynein intermediate chain, causes neuronal atrophy in primary hippocampal neurons. With this cellular model, we are able to find that activation of RAS-RAF-MEK signaling protects against neuronal atrophy induced by DYNC1I1 deficiency, which relies on MEK-dependent autophagy in neuron. Moreover, we further reveal that BRAF also protects against neuronal atrophy induced by mitochondrial impairment. These findings demonstrate protective roles of the RAS-RAF-MEK axis against neuronal atrophy, and imply a new therapeutic target for clinical intervention.
