Notch1 regulated autophagy controls survival and suppressor activity of activated murine T-regulatory cells
Authors: Nimi Marcel
Apurva Sarin
Journal: eLife (2016)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Notch; Signaling; T-cells; apoptosis; autophagy
Affiliations: National Centre for Biological Sciences, Bengaluru, India

Abstract:  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. 

Retracted: No

PubPeer comments:
  , 
 Analysis of original scans is underway and a clarification - duplicate scan or an image of a different plane of the same cell - will be posted as soon as raw data is assessed. It may be noted that other cells in the same row and Panel F (upper row) show mitochondrial phenotypes of cells from the same condition, A mistake was noted in the legend of this figure. In Panels B and C the  NO IL_2 SCR shRNA group (shown in Panel B and C-iv) is a control for shRNA DLL-1 (row 2) and shRNA Atg7 (C-v) transfected cells. These groups were assessed together, which is not explained. While the figure labels are correct, the conditions are incorrectly described in the legend. We are contacting the journal for corrects. The corrections do not change the conclusions of the study. , 
  , 
  , 
  , 
  , 
 #5 The cells shown in the main figure are representations of multiple cells in the pool shown in the supplemental figure. , 
 #6 The error occurred during figure assembly as a template image used for sizing purposes was mistakenly retained when preparing the figure for the Science Signaling 2017 submission. The template used was a panel from the eLife study. Since these are images of Foxp3 detected by immunofluorescence, which does not change in the conditions studied, the mistake went undetected during the submission as well as proofreading stages. The journal has been contacted to request a replacement of the duplicated panel with the correct data, generated when the experiments were performed. , 
 #8  *a template image used for sizing purposes was mistakenly retained when preparing the figure* What are exactly these sizing purposes? Sizing of what? Could Dr. Sarin please elaborate more? , 
 #8 Could you please explain why there is a new cell (red arrow) in only one image? How this happened?  ,