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Hierarchical Regulation of WASP/WAVE Proteins
Open accessAbstract
SUMMARY Members of the Wiskott-Aldrich Syndrome Protein (WASP) family control actin dynamics in eukaryotic cells through stimulating the actin nucleating activity of the Arp2/3 complex. The prevailing paradigm for WASP regulation invokes allosteric relief of autoinhibition by diverse upstream activators. Here we demonstrate an additional level of regulation that is superimposed upon allostery: dimerization increases the affinity of active WASP species for Arp2/3 complex by up to 180-fold, greatly enhancing actin assembly by this system. This finding explains a large and apparently disparate set of observations under a common mechanistic framework. These include WASP activation by the bacterial effector EspFu and a large number of SH3 domain proteins, the effects on WASP of membrane localization/clustering and assembly into large complexes, and cooperativity between different family members. Allostery and dimerization act in hierarchical fashion, enabling WASP/WAVE proteins to integrate different classes of inputs to produce a wide range of cellular actin responses.
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Cites
Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck
Eden, S., Rohatgi, R., Podtelejnikov, A. V., Mann, M., & Kirschner, M. W. (2002) · Nature · doi:10.1038/nature00859 · Cited by 835
Interaction of WASP/Scar proteins with actin and vertebrate Arp2/3 complex
Marchand, J.-B., Kaiser, D. A., Pollard, T. D., & Higgs, H. N. (2001) · Nature Cell Biology · doi:10.1038/35050590 · Cited by 331
Cited by
A nucleator arms race: cellular control of actin assembly
Campellone, K. G., & Welch, M. D. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2867 · Cited by 928
The BAR Domain Superfamily: Membrane-Molding Macromolecules
Frost, A., Unger, V. M., & De Camilli, P. (2009) · Cell · doi:10.1016/j.cell.2009.04.010 · Cited by 574
Structure and control of the actin regulatory WAVE complex
Chen, Z., Borek, D., Padrick, S. B., Gomez, T. S., Metlagel, Z., Ismail, A. M., Umetani, J., Billadeau, D. D., Otwinowski, Z., & Rosen, M. K. (2010) · Nature · doi:10.1038/nature09623 · Cited by 500
Self-citationStoichiometry controls activity of phase-separated clusters of actin signaling proteins
Case, L. B., Zhang, X., Ditlev, J. A., & Rosen, M. K. (2019) · Science · doi:10.1126/science.aau6313 · Cited by 499
Self-citationActin Dynamics at the Leading Edge: From Simple Machinery to Complex Networks
Insall, R. H., & Machesky, L. M. (2009) · Developmental Cell · doi:10.1016/j.devcel.2009.08.012 · Cited by 428
Metadata
- Authors
- Padrick, S. B., Cheng, H.-C., Ismail, A. M., Panchal, S. C., Doolittle, L. K., Kim, S., Skehan, B. M., Umetani, J., Brautigam, C. A., Leong, J. M., & Rosen, M. K.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2008-11
- Volume
- 32
- Issue
- 3
- Pages
- 426-438
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W1982863538
- Cited by
- 203
- References
- 2
- FWCI
- 8.54
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Padrick, S. B., Cheng, H.-C., Ismail, A. M., Panchal, S. C., Doolittle, L. K., Kim, S., Skehan, B. M., Umetani, J., Brautigam, C. A., Leong, J. M., & Rosen, M. K. (2008). Hierarchical Regulation of WASP/WAVE Proteins. Molecular Cell. https://doi.org/10.1016/j.molcel.2008.10.012
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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