气候变化领域集成服务门户(CCPortal): The phosphatidylserine flippase beta-subunit Tmem30a is essential for normal insulin maturation and secretion

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DOI	10.1016/j.ymthe.2021.04.026
	The phosphatidylserine flippase beta-subunit Tmem30a is essential for normal insulin maturation and secretion
	Yang, Yeming; Sun, Kuanxiang; Liu, Wenjing; Li, Xiao; Tian, Wanli; Shuai, Ping; Zhu, Xianjun
通讯作者	Shuai, P ; Zhu, XJ (通讯作者)，Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Chengdu 610072, Sichuan, Peoples R China.
发表日期	2021
ISSN	1525-0016
EISSN	1525-0024
起始页码	2854
结束页码	2872
卷号	29 期号:9
英文摘要	The processing, maturation, and secretion of insulin are under precise regulation, and dysregulation causes profound defects in glucose handling, leading to diabetes. Tmem30a is the b subunit of the phosphatidylserine (PS) flippase, which maintains the membrane asymmetric distribution of PS. Tmem30a regulates cell survival and the localization of subcellular structures and is thus critical to the normal function of multiple physiological systems. Here, we show that conditional knockout of Tmem30a specifically in pancreatic islet b cells leads to obesity, hyperglycemia, glucose intolerance, hyperinsulinemia, and insulin resistance in mice, due to insufficient insulin release. Moreover, we reveal that Tmem30a plays an essential role in clathrin-mediated vesicle transport between the trans Golgi network (TGN) and the plasma membrane (PM), which comprises immature secretory granule (ISG) budding at the TGN. We also find that Tmem30a deficiency impairs clathrin-mediated vesicle budding and thus blocks both insulin maturation in ISGs and the transport of glucose-sensing Glut2 to the PM. Collectively, these disruptions compromise both insulin secretion and glucose sensitivity, thus contributing to impairments in glucose-stimulated insulin secretion. Taken together, our data demonstrate an important role of Tmem30a in insulin maturation and glucose metabolic homeostasis and suggest the importance of membrane phospholipid distribution in metabolic disorders.
关键词	PANCREATIC BETA-CELLS FATTY LIVER-DISEASE TRANS-GOLGI NETWORK PHOSPHOLIPID TRANSLOCATION ENDOPLASMIC-RETICULUM PLASMA-MEMBRANE CDC50 PROTEINS OBESITY ATPASE GENE
语种	英语
WOS研究方向	Biotechnology & Applied Microbiology ; Genetics & Heredity ; Research & Experimental Medicine
WOS类目	Biotechnology & Applied Microbiology ; Genetics & Heredity ; Medicine, Research & Experimental
WOS记录号	WOS:000692597100007
来源期刊	MOLECULAR THERAPY
来源机构	中国科学院西北生态环境资源研究院
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/255180
作者单位	[Yang, Yeming; Shuai, Ping; Zhu, Xianjun] Univ Elect Sci & Technol China, Sch Med, Sichuan Prov Peoples Hosp, Hlth Management Ctr, Chengdu 610072, Sichuan, Peoples R China; [Yang, Yeming; Sun, Kuanxiang; Liu, Wenjing; Li, Xiao; Tian, Wanli; Shuai, Ping; Zhu, Xianjun] Univ Elect Sci & Technol China, Sichuan Prov Key Lab Human Dis Gene Study, Ctr Med Genet, Prenatal Diag Ctr,Sichuan Prov Peoples Hosp, Chengdu 610072, Sichuan, Peoples R China; [Zhu, Xianjun] Chinese Acad Sci, Key Lab Tibetan Med Res, Xining 810008, Qinghai, Peoples R China; [Zhu, Xianjun] Northwest Inst Plateau Biol, Qinghai Prov Key Lab Tibetan Med Res, Xining 810008, Qinghai, Peoples R China; [Shuai, Ping; Zhu, Xianjun] Chinese Acad Med Sci 2019RU026, Res Unit Blindness Prevent, Sichuan Acad Med Sci & Sichuan Prov Peoples Hosp, Chengdu 610072, Sichuan, Peoples R China; [Zhu, Xianjun] Chinese Acad Sci, Nat Prod Res Ctr, Inst Chengdu Biol, Sichuan Translat Med Hosp, Chengdu 610072, Sichuan, Peoples R China; [Zhu, Xianjun] First Peoples Hosp ...
推荐引用方式 GB/T 7714	Yang, Yeming,Sun, Kuanxiang,Liu, Wenjing,et al. The phosphatidylserine flippase beta-subunit Tmem30a is essential for normal insulin maturation and secretion[J]. 中国科学院西北生态环境资源研究院,2021,29(9).
APA	Yang, Yeming.,Sun, Kuanxiang.,Liu, Wenjing.,Li, Xiao.,Tian, Wanli.,...&Zhu, Xianjun.(2021).The phosphatidylserine flippase beta-subunit Tmem30a is essential for normal insulin maturation and secretion.MOLECULAR THERAPY,29(9).
MLA	Yang, Yeming,et al."The phosphatidylserine flippase beta-subunit Tmem30a is essential for normal insulin maturation and secretion".MOLECULAR THERAPY 29.9(2021).