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The WAVE regulatory complex is inhibited

Abstract

The WAVE regulatory complex (WRC) transmits information from the Rac GTPase to the actin nucleator Arp2/3 complex. We have reconstituted recombinant human and Drosophila WRC in several forms and shown that they are inactive toward Arp2/3 complex but can be activated by Rac in a nucleotide-dependent fashion. Our observations identify core components needed for WAVE inhibition, reconcile contradictory existing mechanisms and reveal common regulatory principles for the WAVE/WASP family of proteins.

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Figure 1: WRC is inhibited.
Figure 2: Recombinant WRC can be activated.

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Acknowledgements

We thank D. Jia (Univ. Texas Southwestern Medical Center, Dallas) for assistance with WRC purification, S. Panchal (Univ. Texas Southwestern Medical Center, Dallas) for assistance with ultracentrifugation experiments and L. Doolittle (University of Texas Southwestern Medical Center, Dallas) for sharing reagents. This work was supported by the Howard Hughes Medical Institute and grants from the US National Institutes of Health (R01-GM56322) and Welch Foundation (I–1544). S.B.P. was supported by a fellowship from the National Institutes of Health (1F32 GM06917902).

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Contributions

A.M.I. designed, performed and analyzed experiments and wrote the manuscript; S.B.P. performed equilibrium ultracentrifugation experiments, discussed and analyzed experiments and wrote the manuscript; B.C. performed pulldown experiment; J.U. maintained Sf9 cultures and assisted in cloning and baculovirus production; M.K.R. discussed experiments and wrote the manuscript.

Corresponding author

Correspondence to Michael K Rosen.

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Supplementary Text and Figures

Supplementary Figures 1–3, Supplementary Table 1 and Supplementary Methods (PDF 6346 kb)

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Ismail, A., Padrick, S., Chen, B. et al. The WAVE regulatory complex is inhibited. Nat Struct Mol Biol 16, 561–563 (2009). https://doi.org/10.1038/nsmb.1587

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