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Title: | A mechanical G2 checkpoint controls epithelial cell division through E-cadherin-mediated regulation of Wee1-Cdk1 |
Author: | Donker, Lisa Houtekamer, Ronja Vliem, Marjolein Sipieter, François Canever, Helena Gómez González, Manuel Bosch Padrós, Miquel Pannekoek, Willem-Jan Trepat Guixer, Xavier Borghi, Nicolas Gloerich, Martijn |
Keywords: | Mitosi Cèl·lules epitelials Mitosis Epithelial cells |
Issue Date: | 11-Oct-2022 |
Publisher: | Cell Press |
Abstract: | Epithelial cell divisions are coordinated with cell loss to preserve epithelial integrity. However, how epithelia adapt their rate of cell division to changes in cell number, for instance during homeostatic turnover or wounding, is not well understood. Here, we show that epithelial cells sense local cell density through mechanosensitive E-cadherin adhesions to control G2/M cell-cycle progression. As local cell density increases, tensile forces on E-cadherin adhesions are reduced, which prompts the accumulation of the G2 checkpoint kinase Wee1 and downstream inhibitory phosphorylation of Cdk1. Consequently, dense epithelia contain a pool of cells that are temporarily halted in G2 phase. These cells are readily triggered to divide following epithelial wounding due to the consequent increase in intercellular forces and resulting degradation of Wee1. Our data collectively show that epithelial cell division is controlled by a mechanical G2 checkpoint, which is regulated by cell-density-dependent intercellular forces sensed and transduced by E-cadherin adhesions.Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved. |
Note: | Reproducció del document publicat a: https://doi.org/10.1016/j.celrep.2022.111475 |
It is part of: | Cell Reports, 2022, vol. 41, num. 2 |
URI: | http://hdl.handle.net/2445/191059 |
Related resource: | https://doi.org/10.1016/j.celrep.2022.111475 |
ISSN: | 2211-1247 |
Appears in Collections: | Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC)) |
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2022_CelRep_AMechanicalG2_TrepatX.pdf | 5.38 MB | Adobe PDF | View/Open |
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