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De Novo Generation of Somatic Stem Cells by YAP/TAZ
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Enigma proteins regulate YAP mechanotransduction.

Ahmed Elbediwy1, Hannah Vanyai2, Maria-Del-Carmen Diaz-de-la-Loza2

  • 1Epithelial Biology Laboratory, The Francis Crick Institute, 1 Midland Rd, London NW1 1AT, UK barry.thompson@crick.ac.uk ahmed.elbediwy@crick.ac.uk.

Journal of Cell Science
|November 9, 2018
PubMed
Summary
This summary is machine-generated.

Cellular forces activate YAP by recruiting Enigma proteins to integrin adhesions. These PDLIM proteins bind YAP, promoting its nuclear entry and gene activation during mechanotransduction.

Keywords:
EnigmaHippoIntegrinMechanotransductionPDLIM5PDLIM7YAP

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Area of Science:

  • Cell Biology
  • Mechanobiology
  • Molecular Biology

Background:

  • Human cells sense mechanical stress via integrin adhesions.
  • This stress response involves YAP (Yes-associated protein) and TAZ transcriptional co-activators.
  • The precise mechanism of integrin signaling activating YAP is not fully understood.

Purpose of the Study:

  • To elucidate the role of Enigma and Enigma-like proteins (PDLIM5/7) in integrin-mediated mechanotransduction.
  • To investigate how these proteins regulate YAP nuclear localization and activity.
  • To determine the mechanism by which forces trigger YAP activation.

Main Methods:

  • Silencing of PDLIM5/7 expression.
  • YAP binding assays using PDLIM5/7 C-terminal PDZ-binding motif (PBM).
  • Recruitment of PDLIM5/7 to integrin adhesions and F-actin stress fibers in response to force.
  • Binding of PDLIM5/7 to α-actinin.

Main Results:

  • Integrin-mediated mechanotransduction requires PDLIM5/7 proteins.
  • YAP binds to PDLIM5/7 via its PBM, which is crucial for YAP's nuclear localization and activity.
  • Silencing PDLIM5/7 reduces YAP nuclear localization, tyrosine phosphorylation, and transcriptional activity.
  • PDLIM5/7 proteins are recruited to integrin adhesions and stress fibers by binding to α-actinin under force.

Conclusions:

  • PDLIM5/7 proteins are essential mediators of integrin-driven mechanotransduction.
  • Force-induced recruitment of PDLIM5/7 to integrin adhesions triggers YAP activation.
  • This mechanism highlights a novel pathway for regulating YAP activity in response to mechanical stress.