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ROCK and Dia have opposing effects on adherens junctions downstream of Rho

Nature Cell Biology volume 4, pages 408–415 (2002)Cite this article

Abstract

Adherens junctions (AJs) are crucial for maintaining the integrity of epithelial tissues and are often disrupted during tumour progression. Rho family proteins have been shown to regulate adherens junctions. We find that activation of the effector kinase ROCK and acto-myosin contraction disrupts AJs downstream of Rho. In contrast, signalling through the Rho effector Dia1 is required to ensure a dynamically stable interface between cells and the maintenance of adherens junction complexes. The ability of Dia1 to regulate the actin network is crucial for the localization of adherens junction components to the cell periphery.

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Figure 1: Effect of Rho inhibition on cell junctions.
Figure 2: Rho is required for the stability of the cell periphery.
Figure 3: Dia1 functions downstream from Rho to maintain adherens junction complexes.
Figure 4: Overexpression of RhoC is more effective than RhoA at disrupting adherens junctions.
Figure 5: ROCK and acto-myosin contractility are required downstream of RhoC to disrupt adherens junctions.
Figure 6: Y-27632 promotes adherens junction formation in SW620 colon carcinoma cells.
Figure 7: Opposing pathways downstream of Rho regulating adherens junctions.

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Acknowledgements

E.S. and C.J.M. are funded by Cancer Research UK; C.J.M. is a Gibb Life Fellow of Cancer Research UK. We thank M. Fukata for GFP–α-catenin, A. Alberts for GFP–mDia1ΔN, H. Paterson for help with microscopy, D. Croft and M. Olson for comments on the manuscript.

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  1. Cancer Research UK Centre for Cell and Molecular Biology, Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK

    Erik Sahai & Christopher J. Marshall

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Corresponding author

Correspondence to Christopher J. Marshall.

Supplementary information

Supplementary figure

Figure S1. Effects of Dia mutants on actin and microtubule networks a, HCT116 cells in 1% DCS were injected with expression constructs for GFP-mDia1ΔN, GFPmDia1ΔNK>A or mDia1ΔNΔC. 16 hours after injection the cells were fixed and stained for GFP or myc-epitope to detect exogenous Dia expression, β-tubulin, and F-actin. b, HEK 293 cells were transfected with either mDia1ΔNΔC, RhoAV14 or mDia1ΔNΔC and RhoAV14, 24 hours after transfection cells were fixed and stained for myc-epitope to detect transfected cells and F-actin. (PDF 153 kb)

Supplemetary movie

Movie 1. HCT116 cells in 10% DCS expressing GFP-α-catenin, frames are 60 seconds apart. (AVI 1280 kb)

Supplemetary movie

Movie 2. HCT116 cells in 10% DCS expressing GFP-α-catenin and C3, frames are 60 seconds apart. (AVI 3784 kb)

Supplemetary movie

Movie 3. HCT15 cells in 10% DCS expressing GFP-α-catenin, frames are 60 seconds apart. (AVI 800 kb)

Supplemetary movie

Movie 4. HCT15 cells in 10% DCS expressing GFP-α-catenin and mDia1ΔNΔC, frames are 60 seconds apart. (AVI 2868 kb)

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Sahai, E., Marshall, C. ROCK and Dia have opposing effects on adherens junctions downstream of Rho. Nat Cell Biol 4, 408–415 (2002). https://doi.org/10.1038/ncb796

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