Dynamic multimerization of Dab2-Myosin VI complexes regulates cargo processivity while minimizing cortical actin...

Area of Science:

• Cell Biology
• Biophysics
• Molecular Motors

Background:

• Myosin VI motors transport endocytic cargo through actin networks.
• Stable motor-cargo interactions can disrupt cytoskeletal architecture.
• The role of dynamic motor-cargo binding in transport is unclear.

Purpose of the Study:

• To investigate the role of dynamic multimerization of myosin VI-Dab2 complexes in cargo transport.
• To determine if dynamic association preserves cytoskeletal integrity.
• To understand the kinetics of the Dab2 MIR-myosin VI interaction.

Main Methods:

• Single-molecule kinetic measurements to determine binding affinity and turnover rates.
• Single-molecule motility assays using DNA origami scaffolds.
• Analysis of actin network organization on lipid bilayers with motor-cargo complexes.

Main Results:

• Dab2 MIR binds myosin VI with moderate affinity (184 nM) and high turnover (1 s⁻¹).
• Saturating Dab2-MIR promotes myosin VI homodimerization and processive motility.
• Dynamic Dab2 MIR-myosin VI interactions preserve actin network integrity, unlike constitutive dimers.

Conclusions:

• Dynamic motor-cargo association is crucial for processive cargo transport.
• This dynamic binding prevents disruption of cytoskeletal organization.
• Myosin VI-Dab2 complex dynamics facilitate efficient transport without compromising cellular structure.