The cell migration molecule UNC-53/NAV2 is linked to the ARP2/3 complex by ABI-1

Area of Science:

• Cell Biology
• Neuroscience
• Molecular Biology

Background:

• Cell migration and outgrowth depend on actin cytoskeleton reorganization.
• The ARP2/3 complex nucleates actin filament assembly, but its regulation by guidance cues is unclear.
• UNC-53 and its vertebrate homolog NAV are crucial for cell and neuronal process migration.

Purpose of the Study:

• To identify novel molecular partners of UNC-53 involved in cell migration.
• To elucidate the mechanism by which UNC-53 regulates actin dynamics during cell outgrowth.
• To understand the integration of guidance cues for ARP2/3-mediated remodeling.

Main Methods:

• Identified ABI-1 as a novel binding partner of UNC-53 using biochemical assays.
• Characterized the binding interaction using a restricted calponin homology (CH) domain of UNC-53.
• Analyzed cell migration phenotypes in C. elegans excretory cells, mechanosensory neurons, and motoneurons.
• Utilized RNA interference (RNAi) to assess the roles of ABI-1 interacting proteins in actin dynamics.

Main Results:

• ABI-1 was identified as a novel binding partner of UNC-53.
• A specific calponin homology (CH) domain of UNC-53 mediates binding to ABI-1.
• UNC-53 and ABI-1 share overlapping expression patterns and similar cell migration defects.
• RNAi knockdown of nck-1, wve-1, and arx-2, known ABI-1 interactors, also caused migration defects.

Conclusions:

• UNC-53/NAV2 acts as a scaffold protein, linking ABI-1 to the ARP2/3 complex via its CH domain.
• This interaction is critical for regulating actin cytoskeleton remodeling during cell migration and neuronal outgrowth.
• The findings provide a mechanistic link between guidance cues and actin dynamics through the UNC-53/ABI-1/ARP2/3 pathway.