气候变化领域集成服务门户(CCPortal): β-arrestin–dependent PI(4,5)P2 synthesis boosts GPCR endocytosis

CCPortal

DOI	10.1073/pnas.2011023118
	β-arrestin–dependent PI(4,5)P2 synthesis boosts GPCR endocytosis
	Jung S.-R.; Jiang Y.; Seo J.B.; Chiu D.T.; Hille B.; Koh D.-S.
发表日期	2021
ISSN	00278424
卷号	118 期号:17
英文摘要	β-arrestins regulate many cellular functions including intracellular signaling and desensitization of G protein–coupled receptors (GPCRs). Previous studies show that β-arrestin signaling and receptor endocytosis are modulated by the plasma membrane phosphoinositide lipid phosphatidylinositol-(4, 5)-bisphosphate (PI(4,5)P2). We found that β-arrestin also helped promote synthesis of PI(4,5)P2 and up-regulated GPCR endocytosis. We studied these questions with the Gq-coupled protease-activated receptor 2 (PAR2), which activates phospholipase C, desensitizes quickly, and undergoes extensive endocytosis. Phosphoinositides were monitored and controlled in live cells using lipid-specific fluorescent probes and genetic tools. Applying PAR2 agonist initiated depletion of PI(4,5)P2, which then recovered during rapid receptor desensitization, giving way to endocytosis. This endocytosis could be reduced by various manipulations that depleted phosphoinositides again right after phosphoinositide recovery: PI(4)P, a precusor of PI(4,5)P2, could be depleted at either the Golgi or the plasma membrane (PM) using a recruitable lipid 4-phosphatase enzyme and PI(4,5)P2 could be depleted at the PM using a recruitable 5-phosphatase. Endocytosis required the phosphoinositides. Knock-down of β-arrestin revealed that endogenous β-arrestin normally doubles the rate of PIP5-kinase (PIP5K) after PAR2 desensitization, boosting PI(4,5)P2-dependent formation of clathrin-coated pits (CCPs) at the PM. Desensitized PAR2 receptors were swiftly immobilized when they encountered CCPs, showing a dwell time of ∼90 s, 100 times longer than for unactivated receptors. PAR2/ β-arrestin complexes eventually accumulated around the edges or across the surface of CCPs promoting transient binding of PIP5K-Iγ. Taken together, β-arrestins can coordinate potentiation of PIP5K activity at CCPs to induce local PI(4,5)P2 generation that promotes recruitment of PI(4,5)P2-dependent endocytic machinery. © 2021 National Academy of Sciences. All rights reserved.
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179752
作者单位	Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195, United States; Department of Chemistry, University of Washington, Seattle, WA 98195, United States; Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, 518055, China; Department of Biosciences, Mokpo National University, Jeonnam, 58554, South Korea; Department of Biomedicine, Health and Life Convergence Sciences, Mokpo National University, Jeonnam, 58554, South Korea; Department of Bioengineering, University of Washington, Seattle, WA 98195, United States
推荐引用方式 GB/T 7714	Jung S.-R.,Jiang Y.,Seo J.B.,等. β-arrestin–dependent PI(4,5)P2 synthesis boosts GPCR endocytosis[J],2021,118(17).
APA	Jung S.-R.,Jiang Y.,Seo J.B.,Chiu D.T.,Hille B.,&Koh D.-S..(2021).β-arrestin–dependent PI(4,5)P2 synthesis boosts GPCR endocytosis.Proceedings of the National Academy of Sciences of the United States of America,118(17).
MLA	Jung S.-R.,et al."β-arrestin–dependent PI(4,5)P2 synthesis boosts GPCR endocytosis".Proceedings of the National Academy of Sciences of the United States of America 118.17(2021).