Cellular model of neuronal atrophy induced by DYNC1I1 deficiency reveals protective roles of RAS-RAF-MEK signaling
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 si...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Oxford University Press
2016-08-01
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| Series: | Protein & Cell |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1007/s13238-016-0301-6 |
| _version_ | 1797711263424315392 |
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| author | Zhi-Dong Liu Su Zhang Jian-Jin Hao Tao-Rong Xie Jian-Sheng Kang |
| author_facet | Zhi-Dong Liu Su Zhang Jian-Jin Hao Tao-Rong Xie Jian-Sheng Kang |
| author_sort | Zhi-Dong Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T07:04:28Z |
| format | Article |
| id | doaj.art-c1528aed89484480887075f3d4da72f4 |
| institution | Directory Open Access Journal |
| issn | 1674-800X 1674-8018 |
| language | English |
| last_indexed | 2024-03-12T07:04:28Z |
| publishDate | 2016-08-01 |
| publisher | Oxford University Press |
| record_format | Article |
| series | Protein & Cell |
| spelling | doaj.art-c1528aed89484480887075f3d4da72f42023-09-02T23:32:20ZengOxford University PressProtein & Cell1674-800X1674-80182016-08-017963865010.1007/s13238-016-0301-6Cellular model of neuronal atrophy induced by DYNC1I1 deficiency reveals protective roles of RAS-RAF-MEK signalingZhi-Dong Liu0Su Zhang1Jian-Jin Hao2Tao-Rong Xie3Jian-Sheng Kang4Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of SciencesKey Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of SciencesKey Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of SciencesKey Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of SciencesKey Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of SciencesAbstract 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.http://link.springer.com/article/10.1007/s13238-016-0301-6RAS-RAF-MEK pathwayatrophydynein intermediate chainmitochondriahippocampal neuronautophagy |
| spellingShingle | Zhi-Dong Liu Su Zhang Jian-Jin Hao Tao-Rong Xie Jian-Sheng Kang Cellular model of neuronal atrophy induced by DYNC1I1 deficiency reveals protective roles of RAS-RAF-MEK signaling Protein & Cell RAS-RAF-MEK pathway atrophy dynein intermediate chain mitochondria hippocampal neuron autophagy |
| title | Cellular model of neuronal atrophy induced by DYNC1I1 deficiency reveals protective roles of RAS-RAF-MEK signaling |
| title_full | Cellular model of neuronal atrophy induced by DYNC1I1 deficiency reveals protective roles of RAS-RAF-MEK signaling |
| title_fullStr | Cellular model of neuronal atrophy induced by DYNC1I1 deficiency reveals protective roles of RAS-RAF-MEK signaling |
| title_full_unstemmed | Cellular model of neuronal atrophy induced by DYNC1I1 deficiency reveals protective roles of RAS-RAF-MEK signaling |
| title_short | Cellular model of neuronal atrophy induced by DYNC1I1 deficiency reveals protective roles of RAS-RAF-MEK signaling |
| title_sort | cellular model of neuronal atrophy induced by dync1i1 deficiency reveals protective roles of ras raf mek signaling |
| topic | RAS-RAF-MEK pathway atrophy dynein intermediate chain mitochondria hippocampal neuron autophagy |
| url | http://link.springer.com/article/10.1007/s13238-016-0301-6 |
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