Apical Size Reduction by Macropinocytosis Alleviates Tissue Crowding

Enzo Bresteau, Eve E Suva, Christopher Revell, Osama A Hassan, Aline Grata, Jennifer Sheridan, Jennifer T. Mitchell, Constandina Arvantis, Farida Korobova, Sarah Woolner, Oliver Jensen, Brian Mitchell*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Tissue crowding represents a critical challenge to epithelial tissues, which often respond via the irreversible process of live cell extrusion. We report cell size reduction via macropinocytosis as an alternative mechanism. Macropinocytosis is triggered by tissue crowding via mechanosensory signaling, leading to substantial internalization of apical membrane and driving a reduction in apical cell size that remodels the epithelium to alleviate crowding. We report that this mechanism regulates the long-term organization of developing epithelium in response to proliferation-induced crowding but also serves as an immediate response to acute external compression. In both cases, inhibiting macropinocytosis induces a dramatic increase in cell extrusion suggesting cooperation between cell extrusion and macropinocytosis in response to compression. Our findings implicate macropinocytosis as an important regulator of dynamic epithelial remodeling.

Original languageEnglish
Article number5338
JournalNature Communications
Volume16
DOIs
Publication statusPublished - 23 Jun 2025

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