Arp2/3 is a negative regulator of growth cone translocation

Geraldine A. Strasser, Nazimah Abdul Rahim, Kristyn E. Vanderwaal, Frank B. Gertler, Lorene M. Lanier

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154 Scopus citations

Abstract

Arp2/3 is an actin binding complex that is enriched in the peripheral lamellipodia of fibroblasts, where it forms a network of short, branched actin filaments, generating the protrusive force that extends lamellipodia and drives fibroblast motility. Although it has been assumed that Arp2/3 would play a similar role in growth cones, our studies indicate that Arp2/3 is enriched in the central, not the peripheral, region of growth cones and that the growth cone periphery contains few branched actin filaments. Arp2/3 inhibition in fibroblasts severely disrupts actin organization and membrane protrusion. In contrast, Arp2/3 inhibition in growth cones minimally affects actin organization and does not inhibit lamellipodia protrusion or de novo filopodia formation. Surprisingly, Arp2/3 inhibition significantly enhances axon elongation and causes defects in growth cone guidance. These results indicate that Arp2/3 is a negative regulator of growth cone translocation.

Original languageEnglish (US)
Pages (from-to)81-94
Number of pages14
JournalNeuron
Volume43
Issue number1
DOIs
StatePublished - Jul 8 2004

Bibliographical note

Funding Information:
We are grateful to Drs. Matt Welch, Tadaomi Takenawa, Keith Burridge, Jurgen Wehland, Ravi Salgia, and Mark Kirschner for their generous gifts of antibodies, to Dr. Laura Machesky for the gift of antibodies and DNA constructs, and to Dr. Burt Vogelstein for the gift of AdEasy cloning vectors. We thank Drs. Julian Ng and Liqun Luo for sharing unpublished data. This work was supported by NIH grant #6895154 and a W.M. Keck Distinguished Young Scholar Award to F.B.G. and Minnesota Medical Foundation grant #333-9238-03 and Academic Health Center Seed grant #2003-39 to L.M.L.

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