Critical role of Ena/VASP proteins for filopodia formation in neurons and in function downstream of netrin-1

Cecile Lebrand, Erik W. Dent, Geraldine A. Strasser, Lorene M. Lanier, Matthias Krause, Tatyana M. Svitkina, Gary G. Borisy, Frank B. Gertler

Research output: Contribution to journalArticlepeer-review

266 Scopus citations

Abstract

Ena/VASP proteins play important roles in axon outgrowth and guidance. Ena/VASP activity regulates the assembly and geometry of actin networks within fibroblast lamellipodia. In growth cones, Ena/VASP proteins are concentrated at filopodia tips, yet their role in growth cone responses to guidance signals has not been established. We found that Ena/VASP proteins play a pivotal role in formation and elongation of filopodia along neurite shafts and growth cone. Netrin-1-induced filopodia formation was dependent upon Ena/VASP function and directly correlated with Ena/VASP phosphorylation at a regulatory PKA site. Accordingly, Ena/VASP function was required for filopodial formation from the growth cone in response to global PKA activation. We propose that Ena/VASP proteins control filopodial dynamics in neurons by remodeling the actin network in response to guidance cues.

Original languageEnglish (US)
Pages (from-to)37-49
Number of pages13
JournalNeuron
Volume42
Issue number1
DOIs
StatePublished - Apr 8 2004

Bibliographical note

Funding Information:
This project was initiated and most of the reagents were generated by L.M.L. We thank members of the Gertler lab for helpful discussion and comments on the manuscript. C.L. was a recipient of a fellowship from the EMBO. F.B.G. was supported by a W.M. Keck Distinguished Young Scholar award. This work was supported by NIH grants NS45366 to E.W.D. and GM62431 to G.G.B and by a Cell Migration Consortium grant U54 GM64346 to G.G.B and GM68678 to F.B.G.

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