Coronin-1C and RCC2 guide mesenchymal migration by trafficking Rac1 and controlling GEF exposure.

Area of Science:

• Cell Biology
• Molecular Biology
• Developmental Biology

Background:

• Sustained cell migration through extracellular matrix requires precise localization of protrusive signals.
• Fibronectin contact activates Rac1 at cell protrusion tips, necessitating regulation of its activity for directional movement.

Purpose of the Study:

• To identify molecular interactions that focus active Rac1 to a single protrusion for directed cell migration.
• To elucidate the roles of coronin-1C (Coro1C) and RCC2 in regulating Rac1 activity and cell polarity.

Main Methods:

• Investigated protein interactions between Coro1C, RCC2, and Rac1.
• Utilized RNA interference and morpholinos to deplete Coro1C and RCC2.
• Examined cell migration in 1D and 3D culture systems.
• Assessed neural crest cell migration in developing zebrafish.

Main Results:

• Coro1C facilitates Rac1 release from non-protrusive membrane and its redistribution to the leading edge.
• RCC2 inhibits Rac1 activation outside the protrusive tip, preventing off-axial protrusion.
• Depletion of Coro1C or RCC2 leads to loss of cell polarity and impaired migration.
• In vivo, Coro1C and RCC2 are essential for timely migration of neural crest derivatives.

Conclusions:

• The Rac1-RCC2-Coro1C complex is critical for focusing Rac1 activity to a single protrusion, ensuring directional cell migration.
• This complex plays a vital role in cell polarity maintenance and migration guidance during embryonic development.