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Notch ligand endocytosis generates mechanical pulling force dependent on dynamin, epsins, and actin
Laurence Meloty-Kapella1, Bhupinder Shergill, Jane Kuon
1Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Developmental Cell
|June 5, 2012
Summary
Notch signaling relies on ligand endocytosis, a process involving ubiquitylation and epsins. This mechanism generates mechanical force, driving Notch receptor activation and proteolysis for cellular responses.
Area of Science:
- Cell Biology
- Molecular Biology
- Developmental Biology
Background:
- Notch signaling is crucial for eukaryotic development, mediated by cell surface proteins.
- Ligand endocytosis is implicated in Notch activation, but its precise role is unclear.
- Existing research suggests ubiquitylation and epsins are involved in Notch ligand endocytosis.
Purpose of the Study:
- To elucidate the mechanism of Notch ligand endocytosis.
- To investigate the role of mechanical force in Notch signaling activation.
- To characterize a distinct mode of clathrin-mediated endocytosis in Notch signaling.
Main Methods:
- Utilized a cell-bead optical tweezers system.
- Investigated clathrin-mediated endocytosis pathways.
- Examined the roles of ligand ubiquitylation, epsins, and actin.
Main Results:
- Identified a distinct mode of clathrin-mediated endocytosis dependent on ligand ubiquitylation, epsins, and actin.
- Provided evidence for cell-mediated mechanical force generation during ligand endocytosis.
- Demonstrated that mechanical pulling force from endocytosis activates Notch proteolysis.
Conclusions:
- Ligand endocytosis is a mechanically driven process essential for Notch signaling.
- This distinct endocytic mechanism generates force that induces conformational changes in Notch.
- The findings offer a new perspective on how cell-cell interactions regulate developmental signaling pathways.
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