Notch1 regulated autophagy controls survival and suppressor activity of activated murine T-regulatory cells

Cell survival is one of several processes regulated by the Notch pathway in mammalian cells. Here we report functional outcomes of non-nuclear Notch signaling to activate autophagy, a conserved cellular response to nutrient stress, regulating survival in murine natural T-regulatory cells (Tregs), an...

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Main Authors: Nimi Marcel, Apurva Sarin
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2016-06-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/14023
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spelling doaj-58ff4519f1504fb0ba7a54b9db6124ee2021-05-05T00:25:50ZengeLife Sciences Publications LtdeLife2050-084X2016-06-01510.7554/eLife.14023Notch1 regulated autophagy controls survival and suppressor activity of activated murine T-regulatory cellsNimi Marcel0Apurva Sarin1https://orcid.org/0000-0003-0851-4818National Centre for Biological Sciences, Bengaluru, India; Department of Biology, Manipal University, Manipal, IndiaNational Centre for Biological Sciences, Bengaluru, India; Institute for Stem Cell Biology & Regenerative Medicine, Bengaluru, IndiaCell survival is one of several processes regulated by the Notch pathway in mammalian cells. Here we report functional outcomes of non-nuclear Notch signaling to activate autophagy, a conserved cellular response to nutrient stress, regulating survival in murine natural T-regulatory cells (Tregs), an immune subset controlling tolerance and inflammation. Induction of autophagy required ligand-dependent, Notch intracellular domain (NIC) activity, which controlled mitochondrial organization and survival of activated Tregs. Consistently, NIC immune-precipitated Beclin and Atg14, constituents of the autophagy initiation complex. Further, ectopic expression of an effector of autophagy (Atg3) or recombinant NIC tagged to a nuclear export signal (NIC-NES), restored autophagy and suppressor function in Notch1-/- Tregs. Furthermore, Notch1 deficiency in the Treg lineage resulted in immune hyperactivity, implicating Notch activity in Treg homeostasis. Notch1 integration with autophagy, revealed in these experiments, holds implications for Notch regulated cell-fate decisions governing differentiation.https://elifesciences.org/articles/14023NotchautophagyapoptosisT-cellsSignaling
collection DOAJ
language English
format Article
sources DOAJ
author Nimi Marcel
Apurva Sarin
spellingShingle Nimi Marcel
Apurva Sarin
Notch1 regulated autophagy controls survival and suppressor activity of activated murine T-regulatory cells
eLife
Notch
autophagy
apoptosis
T-cells
Signaling
author_facet Nimi Marcel
Apurva Sarin
author_sort Nimi Marcel
title Notch1 regulated autophagy controls survival and suppressor activity of activated murine T-regulatory cells
title_short Notch1 regulated autophagy controls survival and suppressor activity of activated murine T-regulatory cells
title_full Notch1 regulated autophagy controls survival and suppressor activity of activated murine T-regulatory cells
title_fullStr Notch1 regulated autophagy controls survival and suppressor activity of activated murine T-regulatory cells
title_full_unstemmed Notch1 regulated autophagy controls survival and suppressor activity of activated murine T-regulatory cells
title_sort notch1 regulated autophagy controls survival and suppressor activity of activated murine t-regulatory cells
publisher eLife Sciences Publications Ltd
series eLife
issn 2050-084X
publishDate 2016-06-01
description Cell survival is one of several processes regulated by the Notch pathway in mammalian cells. Here we report functional outcomes of non-nuclear Notch signaling to activate autophagy, a conserved cellular response to nutrient stress, regulating survival in murine natural T-regulatory cells (Tregs), an immune subset controlling tolerance and inflammation. Induction of autophagy required ligand-dependent, Notch intracellular domain (NIC) activity, which controlled mitochondrial organization and survival of activated Tregs. Consistently, NIC immune-precipitated Beclin and Atg14, constituents of the autophagy initiation complex. Further, ectopic expression of an effector of autophagy (Atg3) or recombinant NIC tagged to a nuclear export signal (NIC-NES), restored autophagy and suppressor function in Notch1-/- Tregs. Furthermore, Notch1 deficiency in the Treg lineage resulted in immune hyperactivity, implicating Notch activity in Treg homeostasis. Notch1 integration with autophagy, revealed in these experiments, holds implications for Notch regulated cell-fate decisions governing differentiation.
topic Notch
autophagy
apoptosis
T-cells
Signaling
url https://elifesciences.org/articles/14023
work_keys_str_mv AT nimimarcel notch1regulatedautophagycontrolssurvivalandsuppressoractivityofactivatedmurinetregulatorycells
AT apurvasarin notch1regulatedautophagycontrolssurvivalandsuppressoractivityofactivatedmurinetregulatorycells
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