Hook Adaptors Induce Unidirectional Processive Motility by Enhancing the Dynein-Dynactin Interaction

Area of Science:

• Cell Biology
• Molecular Motors
• Intracellular Trafficking

Background:

• Cytoplasmic dynein is crucial for minus end-directed organelle and vesicle transport.
• Regulation of dynein activity is complex and cargo-specific.
• Hook proteins are implicated in microtubule motor regulation in fungi.

Purpose of the Study:

• To investigate the role of mammalian Hook proteins (Hook1 and Hook3) as potential dynein motor adaptors.
• To determine if Hook proteins regulate dynein-mediated intracellular transport.
• To characterize the mechanism by which Hook proteins interact with dynein.

Main Methods:

• Optogenetic recruitment of Hook proteins to organelles.
• Biochemical assays for protein interactions.
• Single-molecule motility assays using total internal reflection fluorescence microscopy.

Main Results:

• Optogenetic recruitment of Hook proteins rapidly transported peroxisomes to the cell's perinuclear region.
• Hook proteins interact with dynein and dynactin, forming a stable supramolecular complex.
• Hook1 and Hook3 significantly enhanced dynein-driven motility, increasing run length and velocity compared to BICD2.

Conclusions:

• Mammalian Hook proteins function as potent activators of cytoplasmic dynein.
• Hook proteins facilitate organelle-specific dynein regulation for precise intracellular trafficking.
• The N-terminal domain of Hook proteins is essential for complex formation with dynein and dynactin.