Piezo1 channel activates ADAM10 sheddase to regulate Notch1 and gene expression
| Autor: | Vincenza Caolo, David J. Beech, Simon Futers, Laeticia Lichtenstein, Marjolaine Debant, Elizabeth A. V. Jones, Naima Endesh, Gregory Parsonage |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
Metalloproteinase biology Chemistry ADAM10 PIEZO1 Notch signaling pathway Sheddase Transmembrane protein Cell biology 03 medical and health sciences 0302 clinical medicine Gene expression embryonic structures Disintegrin biology.protein cardiovascular system 030217 neurology & neurosurgery 030304 developmental biology |
| DOI: | 10.1101/732370 |
| Popis: | Mechanical force has emerged as a determinant of Notch signalling but the mechanisms of force sensing and coupling to Notch are unclear. Here we propose a role for Piezo1 channels, the recently identified mechanosensors of mammalian systems. Piezo1 channel opening in response to shear stress or a chemical agonist led to activation of a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), a Ca2+-regulated transmembrane sheddase that mediates S2 Notch1 cleavage. Consistent with this observation there was increased Notch1 intracellular domain (NICD) that depended on ADAM10 and the downstream S3 cleavage enzyme, γ-secretase. Endothelial-specific disruption of Piezo1 in mice led to decreased Notch1-regulated gene expression in hepatic vasculature, consistent with prior evidence that Notch1 controls hepatic perfusion. The data suggest Piezo1 as a mechanism for coupling physiological force at the endothelium to ADAM10, Notch1, gene expression and vascular function. |
| Databáze: | OpenAIRE |
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