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

Gagliardi, Paolo Armando; Dobrzyński, Maciej; Jacques, Marc-Antoine; Dessauges, Coralie; Ender, Pascal; Blum, Yannick; Hughes, Robert M; Cohen, Andrew R; Pertz, Olivier (2021). Collective ERK/Akt activity waves orchestrate epithelial homeostasis by driving apoptosis-induced survival. Developmental cell, 56(12), 1712-1726.e6. Elsevier 10.1016/j.devcel.2021.05.007

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Cell Biology
09 Interdisciplinary Units > Microscopy Imaging Center (MIC)

UniBE Contributor:

Gagliardi, Paolo Armando, Jacques, Marc-Antoine Frédéric Roméo, Dessauges, Coralie, Ender, Pascal Peter, Pertz, Olivier

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

1878-1551

Publisher:

Elsevier

Language:

English

Submitter:

Olivier Pertz

Date Deposited:

14 Jun 2021 11:41

Last Modified:

05 Dec 2022 15:51

Publisher DOI:

10.1016/j.devcel.2021.05.007

Related URLs:

PubMed ID:

34081908

Uncontrolled Keywords:

Akt EGFR ERK apoptosis epithelial homeostasis fluorescent biosensors optogenetics signaling dynamics single-cell biology

BORIS DOI:

10.48350/156706

URI:

https://boris.unibe.ch/id/eprint/156706

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