Cellular model of neuronal atrophy induced by DYNC1I1 deficiency reveals protective roles of RAS-RAF-MEK signaling

doi:10.1007/s13238-016-0301-6

Protein Cell

2016, Vol. 7

Issue (9) : 638-650 https://doi.org/10.1007/s13238-016-0301-6

RESEARCH ARTICLE

Cellular model of neuronal atrophy induced by DYNC1I1 deficiency reveals protective roles of RAS-RAF-MEK signaling

Zhi-Dong Liu¹,Su Zhang^1,²,Jian-Jin Hao¹,Tao-Rong Xie¹,Jian-Sheng Kang^1,²(

)

¹. Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200231, China
². University of Chinese Academy of Sciences, Beijing 100049, China

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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.

Keywords RAS-RAF-MEK pathway atrophy dynein intermediate chain mitochondria hippocampal neuron autophagy

Corresponding Author(s): Jian-Sheng Kang

Issue Date: 27 September 2016

Cite this article:

Zhi-Dong Liu,Su Zhang,Jian-Jin Hao, et al. Cellular model of neuronal atrophy induced by DYNC1I1 deficiency reveals protective roles of RAS-RAF-MEK signaling[J]. Protein Cell, 2016, 7(9): 638-650.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-016-0301-6
https://academic.hep.com.cn/pac/EN/Y2016/V7/I9/638

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