Disruption of Tmem30a results in cerebellar ataxia and degeneration of Purkinje cells

doi:10.1038/s41419-018-0938-6

CORC > 成都生物研究所 > 中国科学院成都生物研究所 > 国家天然药物工程技术研究中心 > 天然产物研究

	Disruption of Tmem30a results in cerebellar ataxia and degeneration of Purkinje cells
	Yang, Yeming 4; Sun, Kuanxiang 4; Liu, Wenjing 4; Zhang, Lin 4; Peng, Kun 4; Zhang, Shanshan 4; Li, Shujin 3; Yang, Mu 3; Jiang, Zhilin 2,4; Lu, Fang 4
刊名	CELL DEATH & DISEASE
	2018
卷号	9 页码:899
ISSN号	2041-4889
DOI	10.1038/s41419-018-0938-6
产权排序	2
文献子类	Article
英文摘要	Phospholipids are asymmetrically distributed across mammalian plasma membrane with phosphatidylserine (PS) and phosphatidylethanolamine concentrated in the cytoplasmic leaflet of the membrane bilayer. This asymmetric distribution is dependent on a group of P4-ATPases named PS flippases. The proper transport and function of PS flippases require a beta-subunit transmembrane protein 30 A (TMEM30A). Disruption of PS flippases led to several human diseases. However, the roles of TMEM30A in the central nervous system remain elusive. To investigate the role of Tmem30a in the cerebellum, we developed a Tmem30a Purkinje cell (PC)-specific knockout (KO) mouse model. The Tmem30a KO mice displayed early-onset ataxia and progressive PC death. Deficiency in Tmem30a led to an increased expression of Glial fibrillary acidic protein and astrogliosis in regions with PC loss. Elevated C/EBP homologous protein and BiP expression levels indicated the presence of endoplasmic reticulum stress in the PCs prior to visible cell loss. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis suggested that apoptotic cell death occurred in the cerebellum. Our data demonstrate that loss of Tmem30a in PCs results in protein folding and transport defects, a substantial decrease in dendritic spine density, increased astrogliosis and PC death. Taken together, our data demonstrate an essential role of Tmem30a in the cerebellum PCs.
学科主题	Cell ; Developmental Biology
URL标识	查看原文
WOS关键词	P-TYPE ATPASE ; PUTATIVE AMINOPHOSPHOLIPID TRANSLOCASE ; PHOSPHOLIPID FLIPPASE ; BETA-SUBUNIT ; PROTEIN ; EXPRESSION ; PHOSPHATIDYLSERINE ; MEMBRANE ; CDC50A ; ATP8A2
WOS研究方向	Cell Biology
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000444827800002
内容类型	期刊论文
源URL	[http://210.75.237.14/handle/351003/30600]
专题	国家天然药物工程技术研究中心_天然产物研究
作者单位	1.Institute of Laboratory Animal Sciences, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Chengdu, Sichuan, China 2.Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Chengdu, Sichuan, China; 3.Chengdu Institute of Biology, Sichuan Translational Medicine Research Hospital, Chinese Academy of Sciences,Chengdu, China; 4.Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Sichuan Prov Key Lab Human Dis Gene Study, Chengdu, Sichuan, Peoples R China;
推荐引用方式 GB/T 7714	Yang, Yeming,Sun, Kuanxiang,Liu, Wenjing,et al. Disruption of Tmem30a results in cerebellar ataxia and degeneration of Purkinje cells[J]. CELL DEATH & DISEASE,2018,9:899.
APA	Yang, Yeming.,Sun, Kuanxiang.,Liu, Wenjing.,Zhang, Lin.,Peng, Kun.,...&Zhu, Xianjun.(2018).Disruption of Tmem30a results in cerebellar ataxia and degeneration of Purkinje cells.CELL DEATH & DISEASE,9,899.
MLA	Yang, Yeming,et al."Disruption of Tmem30a results in cerebellar ataxia and degeneration of Purkinje cells".CELL DEATH & DISEASE 9(2018):899.