纤毛
生物
G蛋白偶联受体
内科学
内分泌学
胰高血糖素
胰岛素
信号转导
受体
胰岛
小岛
肠内分泌细胞
细胞生物学
胰腺
激素
内分泌系统
生物化学
医学
作者
Chi-Chang Wu,Keren I. Hilgendorf,R. J. Bevacqua,Yan Hang,János Demeter,Seung K. Kim,Peter K. Jackson
出处
期刊:Genes & Development
[Cold Spring Harbor Laboratory]
日期:2021-08-12
卷期号:35 (17-18): 1243-1255
被引量:28
标识
DOI:10.1101/gad.348261.121
摘要
Multiple G protein-coupled receptors (GPCRs) are expressed in pancreatic islet cells, but the majority have unknown functions. We observed specific GPCRs localized to primary cilia, a prominent signaling organelle, in pancreatic α and β cells. Loss of cilia disrupts β-cell endocrine function, but the molecular drivers are unknown. Using functional expression, we identified multiple GPCRs localized to cilia in mouse and human islet α and β cells, including FFAR4, PTGER4, ADRB2, KISS1R, and P2RY14. Free fatty acid receptor 4 (FFAR4) and prostaglandin E receptor 4 (PTGER4) agonists stimulate ciliary cAMP signaling and promote glucagon and insulin secretion by α- and β-cell lines and by mouse and human islets. Transport of GPCRs to primary cilia requires TULP3, whose knockdown in primary human and mouse islets relocalized ciliary FFAR4 and PTGER4 and impaired regulated glucagon or insulin secretion, without affecting ciliary structure. Our findings provide index evidence that regulated hormone secretion by islet α and β cells is controlled by ciliary GPCRs providing new targets for diabetes.
科研通智能强力驱动
Strongly Powered by AbleSci AI