Calcium Wave Promotes Cell Extrusion

Area of Science:

• Cell Biology
• Developmental Biology
• Tissue Homeostasis

Background:

• Epithelial cells undergo apical extrusion when transformed or apoptotic to maintain tissue homeostasis.
• The molecular mechanisms driving this essential cellular process remain largely unknown.

Purpose of the Study:

• To elucidate the molecular mechanisms regulating apical extrusion of transformed and apoptotic cells from epithelia.
• To identify key signaling pathways involved in cell extrusion.

Main Methods:

• Utilized mammalian cultured epithelial cells and zebrafish embryos.
• Investigated the role of calcium signaling, IP3 receptor, gap junctions, and TRPC1 in cell extrusion.
• Analyzed cellular movements and actin rearrangements during extrusion.

Main Results:

• Observed a calcium wave originating from transformed cells preceding their apical extrusion.
• Demonstrated that this calcium wave triggers and facilitates cell extrusion.
• Identified involvement of IP3 receptor, gap junction, and TRPC1 in calcium wave propagation.
• Showed calcium waves induce polarized cell movement and actin rearrangement in surrounding cells.
• Confirmed calcium wave's role in the apical extrusion of apoptotic cells.

Conclusions:

• Calcium wave is a conserved, general regulatory mechanism for apical cell extrusion.
• This pathway is critical for maintaining epithelial homeostasis by removing damaged or transformed cells.