Spindly is required for rapid migration of human cells

Area of Science:

• Cell Biology
• Molecular Motors
• Cytoskeleton Dynamics

Background:

• Dynein is a vital minus-end-directed microtubule motor in animals, essential for cell division, trafficking, and migration.
• Dynein, along with dynactin and other factors like Bicaudal D, regulates cell polarity, focal adhesion, and microtubule anchoring.
• Spindly protein's role in interphase dynein/dynactin function was previously unknown, despite its known role in mitosis.

Purpose of the Study:

• To investigate the role of Spindly protein in interphase dynein/dynactin function, particularly in cell migration.
• To determine if Spindly is involved in the localization and activity of the dynein/dynactin motor complex during cell migration.

Main Methods:

• Immunofluorescence microscopy to observe Spindly and dynein/dynactin colocalization at the cell cortex and leading edge.
• Cell migration assays using U2OS cells with and without Spindly.
• Rescue experiments with re-expressed Spindly and a dynactin-binding mutant.

Main Results:

• Spindly was found to bind to the cell cortex and microtubule tips, colocalizing with dynein/dynactin at the leading edge of migrating cells.
• U2OS cells lacking Spindly exhibited significantly slower 2D migration compared to control cells.
• While centrosome polarization was unaffected, Spindly re-expression rescued migration defects, whereas a dynactin-binding mutant could not.

Conclusions:

• Spindly plays a critical role in mediating dynein/dynactin's function in cell migration.
• Spindly acts as an adaptor, linking dynein/dynactin to the cell cortex and microtubule tips to facilitate cell movement.
• This study reveals a novel interphase function for Spindly in regulating microtubule motor activity for cell migration.