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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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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1721476333236649984 |