Bresteau Enzo, Suva Eve E, Revell Christopher, Hassan Osama A, Grata Aline, Sheridan Jennifer, Mitchell Jennifer, Arvanitis Constadina, Korobova Farida, Woolner Sarah, Jensen Oliver E, Mitchell Brian
Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Department of Mathematics, University of Manchester, Manchester, UK.
Nat Commun. 2025 Jun 23;16(1):5338. doi: 10.1038/s41467-025-60724-2.
Tissue crowding represents a critical challenge to epithelial tissues, which often respond via the irreversible process of live cell extrusion. We report that apical size reduction via macropinocytosis serves as a malleable and less destructive form of tissue remodeling that can alleviate the need for cell loss. We find that macropinocytosis is triggered by tissue crowding via mechanosensory signaling, leading to substantial internalization of apical membrane. This drives a reduction in apical surface which alleviates crowding. We report that this mechanism regulates the long-term organization of the developing epithelium and controls the timing of proliferation-induced cell extrusion. Additionally, we observe a wave of macropinocytosis in response to acute external compression. In both scenarios, inhibiting macropinocytosis induces a dramatic increase in cell extrusion suggesting cooperation between cell extrusion and macropinocytosis in response to both developmental and external compression. Our findings implicate macropinocytosis as an important regulator of dynamic epithelial remodeling.
组织拥挤对上皮组织构成了严峻挑战,上皮组织通常通过活细胞不可逆挤出的过程做出反应。我们报告称,通过巨胞饮作用使顶端尺寸减小是一种可塑性且破坏性较小的组织重塑形式,可减少细胞丢失的需求。我们发现,组织拥挤通过机械感觉信号触发巨胞饮作用,导致顶端膜大量内化。这促使顶端表面减小,从而缓解拥挤。我们报告称,该机制调节发育中上皮组织的长期组织结构,并控制增殖诱导的细胞挤出的时机。此外,我们观察到在急性外部压迫下会出现一波巨胞饮作用。在这两种情况下,抑制巨胞饮作用都会导致细胞挤出显著增加,这表明在发育和外部压迫反应中,细胞挤出与巨胞饮作用之间存在协同作用。我们的研究结果表明巨胞饮作用是动态上皮重塑的重要调节因子。
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