심명섭 (Duke University) | 한빛사논문 > 한빛사

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Duke University

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Proc. Natl. Acad. Sci. USA, March 30, 2021, 118(13) : e2021942118 | https://doi.org/10.1073/pnas.2021942118 Primary cilia and the reciprocal activation of AKT and SMAD2/3 regulate stretch-induced autophagy in trabecular meshwork cells

Myoung Sup Shim^a, April Nettesheim^a, Angela Dixon^a, and Paloma B. Liton^a,1

^aDepartment of Ophthalmology, Duke Eye Center, Duke University, Durham, NC 27705

¹To whom correspondence may be addressed.

Abstract

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.

autophagy, primary cilia, glaucoma, trabecular meshwork, stretching

논문정보

형식Research article
게재일2021년 03월 (BRIC 등록일 2021-04-06)
연구진국외 연구진
분야 생명과학 > 세포생물학

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