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

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.

Automated summary

Cell death events are essential for eliminating old or damaged cells, but how apoptotic events are organized spatially and temporally to maintain epithelial homeostasis is still unclear. Research has shown that waves of ERK/Akt activity pulses originating from apoptotic cells can act as spatial survival signals, protecting nearby cells from apoptosis for a period of 3-4 hours. At the population level, these waves help maintain epithelial homeostasis in response to environmental insults.