Context-dependent switch in chemo/mechanotransduction via multilevel crosstalk among cytoskeleton-regulated MRTF and TAZ and TGFβ-regulated Smad3

Pam Speight, Michael Kofler, Katalin Szászi and András Kapus ()
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Pam Speight: Keenan Research Centre for Biomedical Science of St Michael’s Hospital, University of Toronto
Michael Kofler: Keenan Research Centre for Biomedical Science of St Michael’s Hospital, University of Toronto
Katalin Szászi: Keenan Research Centre for Biomedical Science of St Michael’s Hospital, University of Toronto
András Kapus: Keenan Research Centre for Biomedical Science of St Michael’s Hospital, University of Toronto

Nature Communications, 2016, vol. 7, issue 1, 1-17

Abstract: Abstract Myocardin-related transcription factor (MRTF) and TAZ are major mechanosensitive transcriptional co-activators that link cytoskeleton organization to gene expression. Despite many similarities in their regulation, their physical and/or functional interactions are unknown. Here we show that MRTF and TAZ associate partly through a WW domain-dependent mechanism, and exhibit multilevel crosstalk affecting each other’s expression, transport and transcriptional activity. Specifically, MRTF is essential for TAZ expression; TAZ and MRTF inhibit each other’s cytosolic mobility and stimulus-induced nuclear accumulation; they antagonize each other’s stimulatory effect on the α-smooth muscle actin (SMA) promoter, which harbours nearby cis-elements for both, but synergize on isolated TEAD-elements. Importantly, TAZ confers Smad3 sensitivity to the SMA promoter. Thus, TAZ is a context-dependent switch during mechanical versus mechano/chemical signalling, which inhibits stretch-induced but is indispensable for stretch+TGFβ-induced SMA expression. Crosstalk between these cytoskeleton-regulated factors seems critical for fine-tuning mechanical and mechanochemical transcriptional programmes underlying myofibroblast transition, wound healing and fibrogenesis.

Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11642

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DOI: 10.1038/ncomms11642

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