학술논문

Caveola mechanotransduction reinforces the cortical cytoskeleton to promote epithelial resilience
Document Type
Report
Source
Molecular Biology of the Cell. November, 2023, Vol. 34 Issue 12, p1b, 14 p.
Subject
Australia
Language
English
ISSN
1059-1524
Abstract
As physical barriers, epithelia must preserve their integrity when challenged by mechanical stresses. Cell--cell junctions linked to the cortical cytoskeleton play key roles in this process, often with mechanotransduction mechanisms that reinforce tissues. Caveolae are mechanosensitive organelles that buffer tension via disassembly. Loss of caveolae, through caveolin-1 or cavin1 depletion, causes activation of PtdIns(4, 5)[P.sub.2] signaling, recruitment of FMNL2 formin, and enhanced-cortical actin assembly. How this equates to physiological responses in epithelial cells containing endogenous caveolae is unknown. Here we examined the effect of mechanically inducing acute disassembly of caveolae in epithelia. We show that perturbation of caveolae, through direct mechanical stress, reinforces the actin cortex at adherens junctions. Increasing interactions with membrane lipids by introducing multiple phosphatidylserine-binding undecad cavin1 (UC1) repeat domains into cavin1 rendered caveolae more stable to mechanical stimuli. This molecular stabilization blocked cortical reinforcement in response to mechanical stress. Cortical reinforcement elicited by the mechanically induced disassembly of caveolae increased epithelial resilience against tensile stresses. These findings identify the actin cortex as a target of caveola mechanotransduction that contributes to epithelial integrity.
INTRODUCTION Epithelia forms many of the biological barriers of the metazoan body. They mediate regulated secretion and absorption and also protect the body from its external environment. Central to this [...]