A novel role for WAVE1 in controlling actin network growth rate and architecture

Meredith O. Sweeney, Agnieszka Collins, Shae B. Padrick, Bruce L. Goode

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Branched actin filament networks in cells are assembled through the combined activities of Arp2/3 complex and different WASP/WAVE proteins. Here we used TIRF and electron microscopy to directly compare for the first time the assembly kinetics and architectures of actin filament networks produced by Arp2/3 complex and dimerized VCA regions of WAVE1, WAVE2, or N-WASP. WAVE1 produced strikingly different networks from WAVE2 or N-WASP, which comprised unexpectedly short filaments. Further analysis showed that the WAVE1-specific activity stemmed from an inhibitory effect on filament elongation both in the presence and absence of Arp2/3 complex, which was observed even at low stoichiometries of WAVE1 to actin monomers, precluding an effect from monomer sequestration. Using a series of VCA chimeras, we mapped the elongation inhibitory effects of WAVE1 to its WH2 ("V") domain. Further, mutating a single conserved lysine residue potently disrupted WAVE1's inhibitory effects. Taken together, our results show that WAVE1 has unique activities independent of Arp2/3 complex that can govern both the growth rates and architectures of actin filament networks. Such activities may underlie previously observed differences between the cellular functions of WAVE1 and WAVE2.

Original languageEnglish (US)
Pages (from-to)495-505
Number of pages11
JournalMolecular biology of the cell
Volume26
Issue number3
DOIs
StatePublished - Feb 1 2015

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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