The desmosome-intermediate filament system facilitates mechanotransduction at adherens junctions for epithelial homeostasis.

Autor:	Nanavati BN; Centre for Cell Biology of Chronic Disease, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia., Noordstra I; Centre for Cell Biology of Chronic Disease, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia., Lwin AKO; Centre for Cell Biology of Chronic Disease, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia., Brooks JW; Centre for Cell Biology of Chronic Disease, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia., Rae J; Centre for Cell Biology of Chronic Disease, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia., Parton RG; Centre for Cell Biology of Chronic Disease, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia; Centre for Microscopy and Microanalysis, The University of Queensland, St. Lucia, QLD 4072, Australia., Verma S; Centre for Cell Biology of Chronic Disease, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia., Duszyc K; Centre for Cell Biology of Chronic Disease, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia., Green KJ; Departments of Pathology and Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL 06011, USA., Yap AS; Centre for Cell Biology of Chronic Disease, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia. Electronic address: a.yap@uq.edu.au.
Jazyk:	angličtina
Zdroj:	Current biology : CB [Curr Biol] 2024 Sep 09; Vol. 34 (17), pp. 4081-4090.e5. Date of Electronic Publication: 2024 Aug 16.
DOI:	10.1016/j.cub.2024.07.074
Abstrakt:	Epithelial homeostasis can be critically influenced by how cells respond to mechanical forces, both local changes in force balance between cells and altered tissue-level forces. ¹ Coupling of specialized cell-cell adhesions to their cytoskeletons provides epithelia with diverse strategies to respond to mechanical stresses. ² ^, ³ ^, ⁴ Desmosomes confer tissue resilience when their associated intermediate filaments (IFs) ² ^, ³ stiffen in response to strain, ⁵ ^, ⁶ ^, ⁷ ^, ⁸ ^, ⁹ ^, ¹⁰ ^, ¹¹ while mechanotransduction associated with the E-cadherin apparatus ¹² ^, ¹³ at adherens junctions (AJs) actively modulates actomyosin by RhoA signaling. Although desmosomes and AJs make complementary contributions to mechanical homeostasis in epithelia, ⁶ ^, ⁸ there is increasing evidence to suggest that these cytoskeletal-adhesion systems can interact functionally and biochemically. ⁸ ^, ¹⁴ ^, ¹⁵ ^, ¹⁶ ^, ¹⁷ ^, ¹⁸ ^, ¹⁹ ^, ²⁰ We now report that the desmosome-IF system integrated by desmoplakin (DP) facilitates active tension sensing at AJs for epithelial homeostasis. DP function is necessary for mechanosensitive RhoA signaling at AJs to be activated when tension was applied to epithelial monolayers. This effect required DP to anchor IFs to desmosomes and recruit the dystonin (DST) cytolinker to apical junctions. DP RNAi reduced the mechanical load that was applied to the cadherin complex by increased monolayer tension. Consistent with reduced mechanical signal strength, DP RNAi compromised assembly of the Myosin VI-E-cadherin mechanosensor that activates RhoA. The integrated DP-IF system therefore supports AJ mechanotransduction by enhancing the mechanical load of tissue tension that is transmitted to E-cadherin. This crosstalk was necessary for efficient elimination of apoptotic epithelial cells by apical extrusion, demonstrating its contribution to epithelial homeostasis. Competing Interests: Declaration of interests A.S.Y. is a member of the Current Biology Advisory Board. (Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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