The intracellular domain of CX3CL1 regulates adult neurogenesis and Alzheimer’s amyloid pathology
The membrane-anchored CX3CL1 is best known to exert its signaling function through binding its receptor CX3CR1. This study demonstrates a novel function that CX3CL1 exerts. CX3CL1 is sequentially cleaved by α-, β-, and γ-secretase, and the released CX3CL1 intracellular domain (CX3CL1-ICD) would tran...
| Main Authors: | , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
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Rockefeller University Press
2020
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| Online Access: | https://hdl.handle.net/1721.1/126401 |
| _version_ | 1811097951060099072 |
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| author | Fan, Qingyuan Gayen, Manoshi Singh, Neeraj Gao, Fan He, Wanxia Hu, Xiangyou Tsai, Li-Huei Yan, Riqiang |
| author2 | Picower Institute for Learning and Memory |
| author_facet | Picower Institute for Learning and Memory Fan, Qingyuan Gayen, Manoshi Singh, Neeraj Gao, Fan He, Wanxia Hu, Xiangyou Tsai, Li-Huei Yan, Riqiang |
| author_sort | Fan, Qingyuan |
| collection | MIT |
| description | The membrane-anchored CX3CL1 is best known to exert its signaling function through binding its receptor CX3CR1. This study demonstrates a novel function that CX3CL1 exerts. CX3CL1 is sequentially cleaved by α-, β-, and γ-secretase, and the released CX3CL1 intracellular domain (CX3CL1-ICD) would translocate into the cell nucleus to alter gene expression due to this back-signaling function. Amyloid deposition and neuronal loss were significantly reduced when membrane-anchored CX3CL1 C-terminal fragment (CX3CL1-ct) was overexpressed in Alzheimer's 5xFAD mouse model. The reversal of neuronal loss in 5xFAD can be attributed to increased neurogenesis by CX3CL1-ICD, as revealed by morphological and unbiased RNA-sequencing analyses. Mechanistically, this CX3CL1 back-signal likely enhances developmental and adult neurogenesis through the TGFβ2/3-Smad2/3 pathway and other genes important for neurogenesis. Induction of CX3CL1 back-signaling may not only be a promising novel mechanism to replenish neuronal loss but also for reducing amyloid deposition for Alzheimer's treatment. |
| first_indexed | 2024-09-23T17:07:34Z |
| format | Article |
| id | mit-1721.1/126401 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T17:07:34Z |
| publishDate | 2020 |
| publisher | Rockefeller University Press |
| record_format | dspace |
| spelling | mit-1721.1/1264012022-09-29T23:50:05Z The intracellular domain of CX3CL1 regulates adult neurogenesis and Alzheimer’s amyloid pathology Fan, Qingyuan Gayen, Manoshi Singh, Neeraj Gao, Fan He, Wanxia Hu, Xiangyou Tsai, Li-Huei Yan, Riqiang Picower Institute for Learning and Memory The membrane-anchored CX3CL1 is best known to exert its signaling function through binding its receptor CX3CR1. This study demonstrates a novel function that CX3CL1 exerts. CX3CL1 is sequentially cleaved by α-, β-, and γ-secretase, and the released CX3CL1 intracellular domain (CX3CL1-ICD) would translocate into the cell nucleus to alter gene expression due to this back-signaling function. Amyloid deposition and neuronal loss were significantly reduced when membrane-anchored CX3CL1 C-terminal fragment (CX3CL1-ct) was overexpressed in Alzheimer's 5xFAD mouse model. The reversal of neuronal loss in 5xFAD can be attributed to increased neurogenesis by CX3CL1-ICD, as revealed by morphological and unbiased RNA-sequencing analyses. Mechanistically, this CX3CL1 back-signal likely enhances developmental and adult neurogenesis through the TGFβ2/3-Smad2/3 pathway and other genes important for neurogenesis. Induction of CX3CL1 back-signaling may not only be a promising novel mechanism to replenish neuronal loss but also for reducing amyloid deposition for Alzheimer's treatment. National Institute on Aging (Grant RF1AG054012) 2020-07-27T19:26:41Z 2020-07-27T19:26:41Z 2019-06 2019-03 2019-10-09T13:00:40Z Article http://purl.org/eprint/type/JournalArticle 0022-1007 1540-9538 https://hdl.handle.net/1721.1/126401 Qingyuan Fan et al. "The intracellular domain of CX3CL1 regulates adult neurogenesis and Alzheimer’s amyloid pathology." Journal of Experimental Medicine 216, 8 (June 2019): 1891–1903 © 2019 Fan et al en http://dx.doi.org/10.1084/jem.20182238 Journal of Experimental Medicine Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Rockefeller University Press Journal of Experimental Medicine (JEM) |
| spellingShingle | Fan, Qingyuan Gayen, Manoshi Singh, Neeraj Gao, Fan He, Wanxia Hu, Xiangyou Tsai, Li-Huei Yan, Riqiang The intracellular domain of CX3CL1 regulates adult neurogenesis and Alzheimer’s amyloid pathology |
| title | The intracellular domain of CX3CL1 regulates adult neurogenesis and Alzheimer’s amyloid pathology |
| title_full | The intracellular domain of CX3CL1 regulates adult neurogenesis and Alzheimer’s amyloid pathology |
| title_fullStr | The intracellular domain of CX3CL1 regulates adult neurogenesis and Alzheimer’s amyloid pathology |
| title_full_unstemmed | The intracellular domain of CX3CL1 regulates adult neurogenesis and Alzheimer’s amyloid pathology |
| title_short | The intracellular domain of CX3CL1 regulates adult neurogenesis and Alzheimer’s amyloid pathology |
| title_sort | intracellular domain of cx3cl1 regulates adult neurogenesis and alzheimer s amyloid pathology |
| url | https://hdl.handle.net/1721.1/126401 |
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