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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Takenawa, T. & Suetsugu, S. Nat. Rev. Mol. Cell Biol. 8, 37–48 (2007).
Billadeau, D.D., Nolz, J.C. & Gomez, T.S. Nat. Rev. Immunol. 7, 131–143 (2007).
Eden, S., Rohatgi, R., Podtelejnikov, A.V., Mann, M. & Kirschner, M.W. Nature 418, 790–793 (2002).
Soderling, S.H. & Scott, J.D. Biochem. Soc. Trans. 34, 73–76 (2006).
Sanz-Moreno, V. et al. Cell 135, 510–523 (2008).
Stradal, T.E. & Scita, G. Curr. Opin. Cell Biol. 18, 4–10 (2006).
Innocenti, M. et al. Nat. Cell Biol. 6, 319–327 (2004).
Kim, Y. et al. Nature 442, 814–817 (2006).
Steffen, A. et al. EMBO J. 23, 749–759 (2004).
Padrick, S.B. et al. Mol. Cell 32, 426–438 (2008).
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).
Author information
Authors and Affiliations
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
Supplementary information
Supplementary Text and Figures
Supplementary Figures 1–3, Supplementary Table 1 and Supplementary Methods (PDF 6346 kb)
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nsmb.1587
This article is cited by
-
Scar/WAVE has Rac GTPase-independent functions during cell wound repair
Scientific Reports (2023)
-
The first quarter of the C-terminal domain of Abelson regulates the WAVE regulatory complex and Enabled in axon guidance
Neural Development (2020)
-
The Small GTPase Rac1 Increases Cell Surface Stiffness and Enhances 3D Migration Into Extracellular Matrices
Scientific Reports (2019)
-
CYRI/FAM49B negatively regulates RAC1-driven cytoskeletal remodelling and protects against bacterial infection
Nature Microbiology (2019)
-
A conformational change within the WAVE2 complex regulates its degradation following cellular activation
Scientific Reports (2017)