A role for actomyosin contractility in Notch signaling

Area of Science:

• Cell Biology
• Developmental Biology
• Biophysics

Background:

• Notch-Delta signaling is vital for cell fate determination and symmetry breaking in developing organisms.
• Unlike other signaling pathways, Notch-Delta requires direct cell-cell contact for activation.
• Emerging evidence suggests mechanical forces, not just ligand binding, may be necessary for Notch signaling.

Purpose of the Study:

• To investigate the role of myosin II-dependent mechanical tension in Notch-Delta signaling.
• To determine if cytoskeletal forces contribute to Notch activation in vivo and in cell culture.

Main Methods:

• Utilized dynamic fluorescence-based reporters to monitor Notch signaling.
• Analyzed the function of myosin II in Notch signaling in developing flies and cell culture models.

Main Results:

• Myosin II is essential for Notch signaling in both signal-sending and receiving cells.
• Myosin II-dependent tension contributes to Notch activation, particularly for signaling at a distance.
• Myosin II is also required for maximal signaling between adjacent cells and in cell culture.

Conclusions:

• Non-muscle myosin II contractility plays a significant role in Notch signaling.
• Mechanical force is critical for the cleavage and activation of the Notch receptor.
• This work establishes a new framework for understanding actomyosin-based mechanosensation in cell signaling.