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Collective ERK/Akt activity waves orchestrate epithelial homeostasis by driving apoptosis-induced survival
Journal article   Open access   Peer reviewed

Collective ERK/Akt activity waves orchestrate epithelial homeostasis by driving apoptosis-induced survival

Paolo Armando Gagliardi, Maciej Dobrzyński, Marc-Antoine Jacques, Coralie Dessauges, Pascal Ender, Yannick Blum, Robert M. Hughes, Andrew R. Cohen and Olivier Pertz
Developmental cell, v 56(12), pp 1712-1726
21 Jun 2021
DOI: https://doi.org/10.1016/j.devcel.2021.05.007
PMID: 34081908
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1016/j.devcel.2021.05.007View
Published, Version of Record (VoR)Open Access (Publisher-Specific),  Open

Abstract

Akt apoptosis EGFR epithelial homeostasis ERK fluorescent biosensors optogenetics signaling dynamics single-cell biology
Cell death events continuously challenge epithelial barrier function yet are crucial to eliminate old or critically damaged cells. How such apoptotic events are spatio-temporally organized to maintain epithelial homeostasis remains unclear. We observe waves of extracellular-signal-regulated kinase (ERK) and AKT serine/threonine kinase (Akt) activity pulses that originate from apoptotic cells and propagate radially to healthy surrounding cells. This requires epidermal growth factor receptor (EGFR) and matrix metalloproteinase (MMP) signaling. At the single-cell level, ERK/Akt waves act as spatial survival signals that locally protect cells in the vicinity of the epithelial injury from apoptosis for a period of 3–4 h. At the cell population level, ERK/Akt waves maintain epithelial homeostasis (EH) in response to mild or intense environmental insults. Disruption of this spatial signaling system results in the inability of a model epithelial tissue to ensure barrier function in response to environmental insults. [Display omitted] •Apoptotic epithelial cells trigger ERK/Akt activity waves in their neighboring cells•EGFR and metalloprotease signaling is required for the ERK/Akt activity wave•Such a signaling wave induces 3–4 h of survival in the neighboring cells•ERK/Akt waves maintain epithelial integrity in response to environmental insults How do epithelia dynamically maintain their integrity in a constantly changing environment? Gagliardi et al. show that apoptotic cells trigger ERK/Akt waves in their neighboring cells inducing survival for 3–4 h. At the cell population scale, this mechanism dynamically protects the epithelium from mild to acute environmental insults.

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Collaboration types
Domestic collaboration
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Web of Science research areas
Cell Biology
Developmental Biology
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