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

TitleEna/VASP regulates mDia2-initiated filopodial length, dynamics, and function.
Publication TypeJournal Article
Year of Publication2014
AuthorsBarzik, M, McClain, LM, Gupton, SL, Gertler, FB
JournalMol Biol Cell
Volume25
Issue17
Pagination2604-19
Date Published2014 Sep 1
ISSN1939-4586
KeywordsAnimals, Cell Adhesion, Cell Adhesion Molecules, Cells, Cultured, Cytoskeletal Proteins, Mice, Microfilament Proteins, Microtubule-Associated Proteins, NADPH Dehydrogenase, Phosphoproteins, Pseudopodia, Signal Transduction
Abstract

Filopodia are long plasma membrane extensions involved in the formation of adhesive, contractile, and protrusive actin-based structures in spreading and migrating cells. Whether filopodia formed by different molecular mechanisms equally support these cellular functions is unresolved. We used Enabled/vasodilator-stimulated phosphoprotein (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 affect filopodia morphology and dynamics independently of one another. 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. Coexpression 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.

DOI10.1091/mbc.E14-02-0712
Alternate JournalMol. Biol. Cell
PubMed ID24989797
PubMed Central IDPMC4148250
Grant List1 Z01 DC000039-17 / DC / NIDCD NIH HHS / United States
1-U54-CA112967 / CA / NCI NIH HHS / United States
GM58801 / GM / NIGMS NIH HHS / United States
R01 GM108970 / GM / NIGMS NIH HHS / United States