Force Triggers YAP Nuclear Entry by Regulating Transport across Nuclear Pores - PubMed (original) (raw)
. 2017 Nov 30;171(6):1397-1410.e14.
doi: 10.1016/j.cell.2017.10.008. Epub 2017 Oct 26.
Ion Andreu 2, Amy E M Beedle 3, Ainhoa Lezamiz 3, Marina Uroz 4, Anita J Kosmalska 5, Roger Oria 5, Jenny Z Kechagia 4, Palma Rico-Lastres 3, Anabel-Lise Le Roux 4, Catherine M Shanahan 6, Xavier Trepat 7, Daniel Navajas 8, Sergi Garcia-Manyes 3, Pere Roca-Cusachs 9
Affiliations
- PMID: 29107331
- DOI: 10.1016/j.cell.2017.10.008
Free article
Force Triggers YAP Nuclear Entry by Regulating Transport across Nuclear Pores
Alberto Elosegui-Artola et al. Cell. 2017.
Free article
Abstract
YAP is a mechanosensitive transcriptional activator with a critical role in cancer, regeneration, and organ size control. Here, we show that force applied to the nucleus directly drives YAP nuclear translocation by decreasing the mechanical restriction of nuclear pores to molecular transport. Exposure to a stiff environment leads cells to establish a mechanical connection between the nucleus and the cytoskeleton, allowing forces exerted through focal adhesions to reach the nucleus. Force transmission then leads to nuclear flattening, which stretches nuclear pores, reduces their mechanical resistance to molecular transport, and increases YAP nuclear import. The restriction to transport is further regulated by the mechanical stability of the transported protein, which determines both active nuclear transport of YAP and passive transport of small proteins. Our results unveil a mechanosensing mechanism mediated directly by nuclear pores, demonstrated for YAP but with potential general applicability in transcriptional regulation.
Keywords: Hippo pathway; atomic force microscopy; mechanosensing; mechanotransduction; molecular mechanical stability; nuclear mechanics; nuclear pores; nuclear transport; rigidity sensing; transcription regulation.
Copyright © 2017 Elsevier Inc. All rights reserved.
Comment in
- Mechanotransduction: Enforcing protein import.
Strzyz P. Strzyz P. Nat Rev Mol Cell Biol. 2017 Dec;18(12):713. doi: 10.1038/nrm.2017.114. Epub 2017 Nov 2. Nat Rev Mol Cell Biol. 2017. PMID: 29093557 No abstract available. - Forcing Entry into the Nucleus.
Lomakin A, Nader G, Piel M. Lomakin A, et al. Dev Cell. 2017 Dec 4;43(5):547-548. doi: 10.1016/j.devcel.2017.11.015. Dev Cell. 2017. PMID: 29207257 Review.
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