Samenvatting
The mechanical regulation of Notch signaling is an emerging area of interest in cell biology. Notch is essential in many physiological processes in which mechanical stress plays an important role. This review provides an overview of the mechanoregulation of Notch signaling in multiple steps of the pathway. First, we discuss the current knowledge on the direct mechanoregulation of Notch receptor maturation and localization to the membrane and the effect of mechanical stress on the Notch components. Next, we explore how ligand-receptor interactions and membrane dynamics are possible subjects to mechano-regulation, emphasizing the role of cytoskeletal interactions, membrane stiffness, and endocytic complex formation. We further delve into the necessity of tension generation for negative regulatory region (NRR) domain unfolding, facilitated by ligand endocytosis and other microforces. Additionally, we examine the indirect mechano-regulation of S2 and S3 cleavages. Finally, we discuss the mechanoregulation of the Notch intracellular domain (NICD) trafficking and nuclear entry and the impact of mechanical stress on heterochromatin dynamics and nuclear NICD interactions. This review aims to draw attention to the intricate interplay between mechanical cues and Notch signaling regulation, offering novel insights into the multifaceted nature of cellular mechanobiology.
| Originele taal-2 | Engels |
|---|---|
| Artikelnummer | 102244 |
| Aantal pagina's | 9 |
| Tijdschrift | Current Opinion in Cell Biology |
| Volume | 85 |
| DOI's | |
| Status | Gepubliceerd - dec. 2023 |
Bibliografische nota
Funding Information:This project has received funding from the European Research Council (ERC) and the European Union's Horizon 2020 research and innovation programme under grant agreement No 771168 (ForceMorph). The research has also been supported by the Academy of Finland , decision numbers #316882 (SPACE), #330411 (SignalSheets), #336355 (Solutions for Health at Åbo Akademi University) and #337531 (InFLAMES Flagship Programme). We have also received funding from the Åbo Akademi University Foundation's Centers of Excellence in Cellular Mechanostasis (CellMech) and Bioelectronic Activation of Cell Functions (BACE).
Funding Information:
The authors thank the ERC, the Academy of Finland, InFLAMES Research Flagship Center and Åbo Akademi University for their financial support. We also thank Kati Kemppainen for her invaluable administrative assistance during the final preparation of the manuscript.