气候变化领域集成服务门户(CCPortal): Primary cilia and the reciprocal activation of AKT and SMAD2/3 regulate stretch-induced autophagy in trabecular meshwork cells

CCPortal

DOI	10.1073/pnas.2021942118
	Primary cilia and the reciprocal activation of AKT and SMAD2/3 regulate stretch-induced autophagy in trabecular meshwork cells
	Shim M.S.; Nettesheim A.; Dixon A.; Liton P.B.
发表日期	2021
ISSN	00278424
卷号	118 期号:13
英文摘要	Activation of autophagy is one of the responses elicited by high intraocular pressure (IOP) and mechanical stretch in trabecular meshwork (TM) cells. However, the mechanosensor and the molecular mechanisms by which autophagy is induced by mechanical stretch in these or other cell types is largely unknown. Here, we have investigated the mechanosensor and downstream signaling pathway that regulate cyclic mechanical stretch (CMS)-induced autophagy in TM cells. We report that primary cilia act as a mechanosensor for CMS-induced autophagy and identified a cross-regulatory talk between AKT1 and noncanonical SMAD2/3 signaling as critical components of primary cilia-mediated activation of autophagy by mechanical stretch. Furthermore, we demonstrated the physiological significance of our findings in ex vivo perfused eyes. Removal of primary cilia disrupted the homeostatic IOP compensatory response and prevented the increase in LC3-II protein levels in response to elevated pressure challenge, strongly supporting a role of primary cilia-mediated autophagy in regulating IOP homeostasis. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Autophagy; Glaucoma; Primary cilia; Stretching; Trabecular meshwork
语种	英语
scopus关键词	AKT1 protein; protein kinase B; Smad2 protein; Smad3 protein; unclassified drug; ANLN gene; Article; AURKA gene; AURKB gene; autophagy (cellular); BIRC5 gene; CCNB1 gene; CDC20 gene; CDKN3 gene; CENPE gene; controlled study; cyclic mechanical stretch induced autophagy; DLGAP5 gene; downstream processing; gene; homeostasis; human; human cell; intraocular pressure; KIF23 gene; mechanotransduction; molecular mechanics; NCAPH gene; NUSAP1 gene; PLK1 gene; PLK4 gene; PRC1 gene; primary cilium; priority journal; receptor cross-talk; signal transduction; SPAG5 gene; TPX2 gene; trabecular meshwork; TYMS gene; UBE2C gene
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/180058
作者单位	Department of Ophthalmology, Duke Eye Center, Duke University, Durham, NC 27705, United States
推荐引用方式 GB/T 7714	Shim M.S.,Nettesheim A.,Dixon A.,et al. Primary cilia and the reciprocal activation of AKT and SMAD2/3 regulate stretch-induced autophagy in trabecular meshwork cells[J],2021,118(13).
APA	Shim M.S.,Nettesheim A.,Dixon A.,&Liton P.B..(2021).Primary cilia and the reciprocal activation of AKT and SMAD2/3 regulate stretch-induced autophagy in trabecular meshwork cells.Proceedings of the National Academy of Sciences of the United States of America,118(13).
MLA	Shim M.S.,et al."Primary cilia and the reciprocal activation of AKT and SMAD2/3 regulate stretch-induced autophagy in trabecular meshwork cells".Proceedings of the National Academy of Sciences of the United States of America 118.13(2021).