Force triggers YAP nuclear entry by regulating transport across nuclear pores
Authors list
Alberto Elosegui Artola Ion Andreu Amy EM Beedle Ainhoa Lezamiz Marina Uroz Anita J Kosmalska Roger Oria Jenny Z Kechagia Palma Rico-Lastres Anabel-Lise Le Roux Catherine M Shanahan Xavier Trepat Daniel Navajas Sergi Garcia-Manyes Pere Roca-CusachsAbstract
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.
Journal details
Journal Cell
Volume 171
Issue number 6
Pages 1397-1410.e14
Available online
Publication date
Full text links
Publisher website (DOI) 10.1016/j.cell.2017.10.008
Europe PubMed Central 29107331
Pubmed 29107331
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