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Scientific article
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The mechano-sensitive response of β1 integrin promotes SRC-positive late endosome recycling and activation of Yes-associated protein

Published inJournal of Biological Chemistry, vol. 295, no. 39, p. 13474-13487
Publication date2020
Abstract

Yes-associated protein (YAP) signaling has emerged as a crucial pathway in several normal and pathological processes. Although the main upstream effectors that regulate its activity have been extensively studied, the role of the endosomal system has been far less characterized. Here, we identified the late endosomal/lysosomal adaptor MAPK and mTOR activator (LAMTOR) complex as an important regulator of YAP signaling in a preosteoblast cell line. We found that p18/LAMTOR1-mediated peripheral positioning of late endosomes allows delivery of SRC proto-oncogene, nonreceptor tyrosine kinase (SRC) to the plasma membrane and promotes activation of an SRC-dependent signaling cascade that controls YAP nuclear shuttling. Moreover, β1 integrin engagement and mechano-sensitive cues, such as external stiffness and related cell contractility, controlled LAMTOR targeting to the cell periphery and thereby late endosome recycling and had a major impact on YAP signaling. Our findings identify the late endosome recycling pathway as a key mechanism that controls YAP activity and explains YAP mechano-sensitivity.

Keywords
  • Animals
  • Cell Cycle Proteins/deficiency/metabolism
  • Cell Line
  • Endosomes/metabolism
  • HEK293 Cells
  • Humans
  • Integrin beta1/metabolism
  • Mice
  • Mice
  • Knockout
  • Signal Transduction
  • Transcription Factors/deficiency/metabolism
  • Src-Family Kinases/deficiency/metabolism
Citation (ISO format)
BLOCK, Marc R et al. The mechano-sensitive response of β1 integrin promotes SRC-positive late endosome recycling and activation of Yes-associated protein. In: Journal of Biological Chemistry, 2020, vol. 295, n° 39, p. 13474–13487. doi: 10.1074/jbc.RA120.013503
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Article (Published version)
Identifiers
ISSN of the journal0021-9258
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