Arginase-II activates mTORC1 through myosin-1b in vascular cell senescence and apoptosis

Cell Death & Disease
Yi YuXiu-Fen Ming

Abstract

Type-II L-arginine:ureahydrolase, arginase-II (Arg-II), is shown to activate mechanistic target of rapamycin complex 1 (mTORC1) pathway and contributes to cell senescence and apoptosis. In an attempt to elucidate the underlying mechanism, we identified myosin-1b (Myo1b) as a mediator. Overexpression of Arg-II induces re-distribution of lysosome and mTOR but not of tuberous sclerosis complex (TSC) from perinuclear area to cell periphery, dissociation of TSC from lysosome and activation of mTORC1-ribosomal protein S6 kinase 1 (S6K1) pathway. Silencing Myo1b prevents all these alterations induced by Arg-II. By overexpressing Myo1b or its mutant with point mutation in its pleckstrin homology (PH) domain we further demonstrate that this effect of Myo1b is dependent on its PH domain that is required for Myo1b-lysosome association. Notably, Arg-II promotes association of Myo1b with lysosomes. In addition, we show that in senescent vascular smooth muscle cells with elevated endogenous Arg-II, silencing Myo1b prevents Arg-II-mediated lysosomal positioning, dissociation of TSC from lysosome, mTORC1 activation and cell apoptosis. Taken together, our study demonstrates that Myo1b mediates the effect of Arg-II in activating mTORC1-S6K1 thro...Continue Reading

References

Apr 17, 1997·Biochemical and Biophysical Research Communications·T GotohM Mori
Mar 21, 1998·Biochimica Et Biophysica Acta·J PerozichS M Morris
May 8, 1999·Molecular Biology of the Cell·G RaposoE Coudrier
Oct 13, 2005·Journal of Cell Science·Laura Salas-CortesEvelyne Coudrier
Apr 8, 2006·Current Hypertension Reports·Zhihong Yang, Xiu-Fen Ming
Apr 26, 2007·Physiological Genomics·Hongyu QiuChristophe Depre
Mar 1, 2008·Circulation Research·Sungwoo RyooDan E Berkowitz
May 18, 2010·Trends in Cell Biology·Russell E McConnell, Matthew J Tyska
Jul 9, 2010·The Journal of Biological Chemistry·Shigeru Komaba, Lynne M Coluccio
Dec 21, 2010·Molecular Biology of the Cell·Juliane P CavistonErika L F Holzbaur
Mar 12, 2011·Nature Cell Biology·Viktor I KorolchukDavid C Rubinsztein
Oct 7, 2011·Acta histochemica·Sungyoung ChoiTaekyun Shin
Apr 17, 2012·Cell·Mathieu Laplante, David M Sabatini
Feb 18, 2014·Cell·Constantinos DemetriadesAurelio A Teleman
Jul 9, 2014·Proceedings of the National Academy of Sciences of the United States of America·Elma ZaganjorMelanie H Cobb
Apr 1, 2015·Proceedings of the National Academy of Sciences of the United States of America·Andreas JeschkeAlbert Haas
Feb 13, 2016·Nature Communications·Constantinos DemetriadesAurelio A Teleman

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Citations

Nov 19, 2020·Cardiovascular Research·Véronique RegnaultPatrick Lacolley
Mar 7, 2021·Journal of Personalized Medicine·Marta Barrera-CondePatricia Robledo
Apr 10, 2021·Biochemistry. Biokhimii︠a︡·Jennet T MammedovaEleonora A Starikova

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Methods Mentioned

BETA
GTPase
PCR
Transfection
Infrared Imaging
confocal microscopy

Software Mentioned

Fiji
NIH Image

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis