WASP and SCAR are evolutionarily conserved in actin-filled pseudopod-based motility

Area of Science:

• Cell biology
• Evolutionary biology
• Biochemistry

Background:

• Eukaryotic cells exhibit diverse migration modes crucial for development and disease.
• Understanding the molecular basis and evolutionary origins of cell migration is essential.
• A specific migration mode, termed 'α-motility,' is characterized by actin-filled pseudopods.

Purpose of the Study:

• To define the molecular markers and evolutionary history of α-motility.
• To investigate the roles of WASP and SCAR/WAVE proteins in pseudopod formation.
• To establish a genetic signature for α-motility.

Main Methods:

• Genomic data mining to identify conserved genes associated with pseudopod formation.
• Experimental depletion of WASP in human neutrophils to assess its function.
• Microscopic observation of cell migration and actin polymerization dynamics.
• Comparative analysis across different eukaryotic species, including chytrid fungi.

Main Results:

• Genomic analysis revealed that only organisms possessing both WASP and SCAR/WAVE possess actin-filled pseudopods.
• WASP depletion impaired actin polymerization, pseudopod formation, and migration in human neutrophils.
• WASP and WAVE proteins were observed to colocalize in dynamic cellular structures.
• The co-occurrence of WASP and SCAR accurately predicted α-motility in chytrid fungi, which exhibited rapid crawling (>30 µm/min).

Conclusions:

• WASP and SCAR/WAVE proteins are key genetic components of α-motility.
• The combined presence of WASP and SCAR/WAVE serves as a reliable genetic marker for this migration mode.
• α-motility represents a widely distributed eukaryotic cell crawling strategy with a likely single evolutionary origin.