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

Molecular biology of the cell

PubMedID: 24989797

Barzik M, McClain LM, Gupton SL, Gertler FB. Ena/VASP regulates mDia2-initiated filopodial length, dynamics, and function. Mol Biol Cell. 2014;.
Filopodia are long plasma membrane extensions involved in the formation of adhesive, contractile, and protrusive actin-based structures in spreading and migrating cells. Whether or not filopodia formed by different molecular mechanisms equally support these cellular functions is unresolved. We used Ena/VASP-deficient MV(D7) fibroblasts, which are also devoid of endogenous mDia2, as a model system to investigate how these different actin regulatory proteins impact filopodia morphology and dynamics independently of the other. Filopodia initiated by either Ena/VASP or mDia2 contained similar molecular inventory, but differed significantly in parameters such as number, length, F-actin organization, lifetime, and protrusive persistence. Moreover, in the absence of Ena/VASP, filopodia generated by mDia2 did not support initiation of integrin-dependent signaling cascades required for adhesion and subsequent lamellipodial extension, thereby causing a defect in early cell spreading. Co-expression of VASP with constitutively active mDia2(M/A) rescued these early adhesion defects. We conclude that Ena/VASP and mDia2 support the formation of filopodia with significantly distinct properties, and that Ena/VASP regulates mDia2-initiated filopodial morphology, dynamics, and function.