Ena/VASP regulates mDia2-initiated filopodial length, dynamics, and function

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Filopodia are crucial actin-based cell extensions involved in cell migration and adhesion.
• The specific roles of different actin regulators, such as Enabled/vasodilator-stimulated phosphoprotein (Ena/VASP) and mDia2, in filopodia formation and function are not fully understood.

Purpose of the Study:

• To investigate how Ena/VASP and mDia2 independently influence filopodia morphology, dynamics, and function.
• To determine if filopodia generated by different molecular mechanisms equally support cellular functions like adhesion and spreading.

Main Methods:

• Utilized Enabled/vasodilator-stimulated phosphoprotein (Ena/VASP)-deficient fibroblasts also lacking mDia2 as a model system.
• Analyzed filopodia characteristics including number, length, F-actin organization, lifetime, and protrusive persistence.
• Assessed the initiation of integrin-dependent signaling and early cell spreading defects.

Main Results:

• Filopodia initiated by Ena/VASP or mDia2 shared molecular inventory but differed significantly in morphology and dynamics.
• In Ena/VASP-deficient cells, mDia2-initiated filopodia failed to support integrin-dependent signaling, impairing cell spreading.
• Coexpression of VASP with active mDia2 rescued these adhesion defects.

Conclusions:

• Ena/VASP and mDia2 generate filopodia with distinct properties, affecting their morphology, dynamics, and functional outcomes.
• Ena/VASP plays a regulatory role in mDia2-initiated filopodia, influencing their function in cell adhesion and spreading.