Reticulon 3 attenuates the clearance of cytosolic prion aggregates by inhibiting autophagy
文献类型：期刊论文
| 作者 | Chen, Rui1,2; Jin, Rui3; Wu, Lu1,2; Ye, Xiaofei1,2; Yang, Yi1,2; Luo, Kan1,2; Wang, Wenxi1,2; Wu, Di1,2; Ye, Xing1,2; Huang, Liqin1,2 |
| 刊名 | Autophagy
 |
| 出版日期 | 2011-02-01 |
| 卷号 | 7期号:2页码:205-216 |
| 关键词 | Prion Er stress Rtn3 Autophagy Ups Apoptosis |
| ISSN号 | 1554-8627 |
| DOI | 10.4161/auto.7.2.14197 |
| 通讯作者 | Xiao, gengfu(xiaogf@wh.iov.cn) |
| 英文摘要 | Autophagy plays an important role in targeting cellular proteins, protein aggregates and organelles for degradation for cell survival. autophagy dysfunction has been extensively described in neurodegenerative conditions linked to protein misfolding and aggregation. however, the role of autophagy in the prion disease process is unclear. here, we show that when expressed in mouse neuroblastoma n2a cells, cytoplasmic prp (cyprp) aggregates lead to endoplasmic reticulum stress (er stress), activation of reticulon 3 (rtn3), impairment of ubiquitin-proteasome system (ups), induction of autophagy and apoptosis. rtn3 belongs to the reticulon family with the highest expression in the brain and rtn3 is often activated under er stress. to assess the function of rtn3 in pathological conditions involving cyprp protein misfolding, we knocked down the expression of rtn3 in cyprp-transfected cells; unexpectedly, the inhibition of expression of rtn3 enhances the induction of autophagy resulted from cyprp aggregates, and the process is mediated by the enhanced interaction between bcl-2 and beclin 1 promoted by rtn3, which enhances bcl-2-mediated inhibition of beclin 1-dependent autophagy. furthermore, downregulation of rtn3 promoted the clearance of cyprp aggregates, allowed the activity of the ups to resume, and alleviated er stress; ultimately, apoptosis due to the cyprp aggregates was inhibited. together, these data suggest that rtn3 negatively regulates autophagy to block the clearance of cyprp aggregates and provide a clue regarding the potential to induce autophagy for the treatment of prion disease and other neurodegenerative diseases such as parkinson disease (pd), alzheimer disease (ad) and huntington disease (hd). |
| WOS关键词 | CHAPERONE-MEDIATED AUTOPHAGY ; ALZHEIMERS-DISEASE ; ALPHA-SYNUCLEIN ; INFECTED CELLS ; PROTEIN ; STRESS ; BCL-2 ; DEGRADATION ; INDUCTION ; NEURODEGENERATION |
| WOS研究方向 | Cell Biology |
| WOS类目 | Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000286802800007 |
| 出版者 | LANDES BIOSCIENCE |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2375894 |
| 专题 | 武汉病毒研究所 |
| 通讯作者 | Xiao, Gengfu |
| 作者单位 | 1.Wuhan Univ, Coll Life Sci, State Key Lab Virol, Wuhan 430072, Peoples R China 2.Wuhan Univ, Coll Life Sci, Modern Virol Res Ctr, Wuhan 430072, Peoples R China 3.Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chen, Rui,Jin, Rui,Wu, Lu,et al. Reticulon 3 attenuates the clearance of cytosolic prion aggregates by inhibiting autophagy[J]. Autophagy,2011,7(2):205-216. |
| APA | Chen, Rui.,Jin, Rui.,Wu, Lu.,Ye, Xiaofei.,Yang, Yi.,...&Xiao, Gengfu.(2011).Reticulon 3 attenuates the clearance of cytosolic prion aggregates by inhibiting autophagy.Autophagy,7(2),205-216. |
| MLA | Chen, Rui,et al."Reticulon 3 attenuates the clearance of cytosolic prion aggregates by inhibiting autophagy".Autophagy 7.2(2011):205-216. |
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来源：武汉病毒研究所
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