Tmem30a deficiency leads to retinal rod bipolar cell degeneration
文献类型：期刊论文
| 作者 | Yang, Yeming1; Liu, Wenjing1 ; Sun, Kuanxiang1; Jiang, Li1,2,3; Zhu, Xianjun1,2,3,4,5,6
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| 刊名 | JOURNAL OF NEUROCHEMISTRY
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| 出版日期 | 2019-02-01 |
| 卷号 | 148期号:3页码:400-412 |
| 关键词 | bipolar cell phosphatidylserine flippase retinal degeneration TMEM30A |
| ISSN号 | 0022-3042 |
| DOI | 10.1111/jnc.14643 |
| 通讯作者 | Zhu, Xianjun(xjzhu@uestc.edu.cn) |
| 英文摘要 | Phospholipids are asymmetrically distributed across the mammalian plasma membrane, with phosphatidylserine (PS) and phosphatidylethanolamine concentrated in the cytoplasmic leaflet of the membrane bilayer and phosphatidylcholine in the exoplasmic leaflet. This asymmetric distribution is dependent on a group of P4 ATPases called PS flippases. The proper transport and function of PS flippases require a beta-subunit transmembrane protein 30A (TMEM30A). Disruption of PS flippases leads to several human diseases. Tmem30a is essential for photoreceptor survival. However, the roles of Tmem30a in the retinal rod bipolar cells (RBC) remain elusive. To investigate the role of Tmem30a in the RBCs, we generated a RBC-specific Tmem30a knockout (cKO) mouse model using PCP2-Cre line. The Tmem30a cKO mice exhibited defect in RBC function and progressive RBC death. PKC alpha staining of retinal cryosections from cKO mice revealed a remarkable dendritic sprouting of rod bipolar cells during the early degenerative process. Immunostaining analysis of PSD95 and mGluT6 expression demonstrated that rod bipolar cells in Tmem30a cKO retinas exhibited aberrant dendritic sprouting as a result of impaired synaptic efficacy, which implied a crucial role for Tmem30a in synaptic transmission in the retina. In addition, loss of Tmem30a led to reactive gliosis with increased expression of glial fibrillary acidic protein and CD68. TUNEL staining suggested that apoptotic cell death occurred in the retinal inner nuclear layer (INL). Our data show that loss of Tmem30a in RBCs results in dendritic sprouting of rod bipolar cells, increased astrogliosis and RBC death. Taken together, our studies demonstrate an essential role for Tmem30a in the retinal bipolar cells. |
| WOS关键词 | PHOSPHOLIPID FLIPPASE ; SUBCELLULAR-LOCALIZATION ; TRANSGENE EXPRESSION ; LIPID ASYMMETRY ; CDC50 PROTEINS ; BETA-SUBUNIT ; ATP8A2 GENE ; PHOSPHATIDYLSERINE ; TRANSLOCATION ; DISRUPTION |
| 资助项目 | Natural Science Foundation of China[81770950] ; Natural Science Foundation of China[81470668] ; Natural Science Foundation of China[81670893] ; Natural Science Foundation of China[2015CB554100] ; Department of Science and Technology of Sichuan Province[2016TD0009] ; Department of Science and Technology of Sichuan Province[2014FZ0124] ; Department of Science and Technology of Sichuan Province[2017TJPT0010] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Neurosciences & Neurology |
| 语种 | 英语 |
| WOS记录号 | WOS:000456593300006 |
| 出版者 | WILEY |
| 资助机构 | Natural Science Foundation of China ; Department of Science and Technology of Sichuan Province |
| 源URL | [http://ir.imde.ac.cn/handle/131551/24961]  |
| 专题 | 中国科学院水利部成都山地灾害与环境研究所 |
| 通讯作者 | Zhu, Xianjun |
| 作者单位 | 1.Univ Elect Sci & Technol China, Sch Med, Sichuan Prov Peoples Hosp, Sichuan Prov Key Lab Human Dis Gene Study, Chengdu, Sichuan, Peoples R China 2.Sichuan Acad Med Sci, Inst Lab Med, Chengdu, Sichuan, Peoples R China 3.Sichuan Prov Peoples Hosp, Chengdu, Sichuan, Peoples R China 4.Shangqiu First Municipal Peoples Hosp, Dept Ophthalmol, Shangqiu, Henan, Peoples R China 5.Chinese Acad Sci, Inst Chengdu Biol, Chengdu, Sichuan, Peoples R China 6.Chinese Acad Sci, Sichuan Translat Med Hosp, Chengdu, Sichuan, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yang, Yeming,Liu, Wenjing,Sun, Kuanxiang,et al. Tmem30a deficiency leads to retinal rod bipolar cell degeneration[J]. JOURNAL OF NEUROCHEMISTRY,2019,148(3):400-412. |
| APA | Yang, Yeming,Liu, Wenjing,Sun, Kuanxiang,Jiang, Li,&Zhu, Xianjun.(2019).Tmem30a deficiency leads to retinal rod bipolar cell degeneration.JOURNAL OF NEUROCHEMISTRY,148(3),400-412. |
| MLA | Yang, Yeming,et al."Tmem30a deficiency leads to retinal rod bipolar cell degeneration".JOURNAL OF NEUROCHEMISTRY 148.3(2019):400-412. |
入库方式： OAI收割
来源：成都山地灾害与环境研究所
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