The Nogo receptor inhibits proliferation, migration and axonal extension by transcriptionally regulating WNK1 in PC12 cells
| Autor: | Yongqin Kuang, Si-Xun Yu, Ziyi Zhao, Hai-Feng Shu, Xin Chen, Jing-min Cheng, Tao Yang, Song Li, Kai Zhao |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Nogo Receptors Cell Biology Transfection PC12 Cells Sincalide 03 medical and health sciences 0302 clinical medicine WNK Lysine-Deficient Protein Kinase 1 Downregulation and upregulation Cell Movement Nerve Growth Factor medicine Transcriptional regulation Animals RNA Messenger Receptor Cell Proliferation Gene knockdown Kinase General Neuroscience Regeneration (biology) WNK1 Axons Rats Cell biology 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Cancer research 030217 neurology & neurosurgery |
| Zdroj: | NeuroReport. 28:533-539 |
| ISSN: | 0959-4965 |
| DOI: | 10.1097/wnr.0000000000000800 |
| Popis: | Neuronal regeneration and axonal regrowth mechanisms in the injured mammalian central nervous system are largely unknown. As part of a major pathway for inhibiting axonal regeneration, activated neuronal glycosylphosphatidylinositol-anchored Nogo receptor (NgR) interacts with LINGO-1 and p75NTR to form a complex at the cell surface. However, it was found in our previous report that upregulation of NgR stimulated by injury plays a key role in neuronal regeneration in the neonatal cortex freeze-lesion model, but its downstream signalling remains elusive. In the present study, the novel regulatory role of NgR in a serine-threonine kinase WNK1 was identified. NgR's transcriptional regulation of WNK1 was identified by RT-qPCR and semiquantitative western blot after the overexpression or knockdown of NgR, and the regulation is specific to WNK1, which is not the same for its family members, WNK2, WNK3 and WNK4. Furthermore, NgR inhibition by NEP fails to affect WNK1, which indicates that WNK1 functions outside of the Nogo-A/NgR pathway. By performing a proliferation, migration and axonal extension assay, we also identified that overexpressed NgR critically regulated these processes and impairment by overexpressing NgR was rescued with coexpression of WNK1, indicating the partial role of WNK1 in NgR-mediated morphological regulation. Our study identifies a separation of functions for the NgR-regulated WNK1 in mediating proliferation, migration and axonal extension in PC12 cells as well as a specific regulatory role between NgR and WNK1 that is important for recovery from central nervous system injury. |
| Databáze: | OpenAIRE |
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