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Tmem30a deficiency leads to retinal rod bipolar cell degeneration
Yang, Yeming1; Liu, Wenjing1; Sun, Kuanxiang1; Jiang, Li1,2,3; Zhu, Xianjun1,2,3,4,5,6
Corresponding AuthorZhu, Xianjun(xjzhu@uestc.edu.cn)
2019-02-01
Source PublicationJOURNAL OF NEUROCHEMISTRY
ISSN0022-3042
Volume148Issue:3Pages:400-412
AbstractPhospholipids 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.
Keywordbipolar cell phosphatidylserine flippase retinal degeneration TMEM30A
DOI10.1111/jnc.14643
Indexed BySCI
WOS KeywordPHOSPHOLIPID FLIPPASE ; SUBCELLULAR-LOCALIZATION ; TRANSGENE EXPRESSION ; LIPID ASYMMETRY ; CDC50 PROTEINS ; BETA-SUBUNIT ; ATP8A2 GENE ; PHOSPHATIDYLSERINE ; TRANSLOCATION ; DISRUPTION
Language英语
Funding ProjectNatural 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 Research AreaBiochemistry & Molecular Biology ; Neurosciences & Neurology
WOS SubjectBiochemistry & Molecular Biology ; Neurosciences
WOS IDWOS:000456593300006
Funding OrganizationNatural Science Foundation of China ; Department of Science and Technology of Sichuan Province
PublisherWILEY
Citation statistics
Document Type期刊论文
Identifierhttp://ir.imde.ac.cn/handle/131551/24962
Collection中国科学院水利部成都山地灾害与环境研究所
Corresponding AuthorZhu, Xianjun
Affiliation1.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
Recommended Citation
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.
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