Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck
Abstract
Rac signalling to actin -- a pathway that is thought to be mediated by the protein Scar/WAVE (WASP (Wiskott-Aldrich syndrome protein)-family verprolin homologous protein -- has a principal role in cell motility. In an analogous pathway, direct interaction of Cdc42 with the related protein N-WASP stimulates actin polymerization. For the Rac-WAVE pathway, no such direct interaction has been identified. Here we report a mechanism by which Rac and the adapter protein Nck activate actin nucleation through WAVE1. WAVE1 exists in a heterotetrameric complex that includes orthologues of human PIR121 (p53-inducible messenger RNA with a relative molecular mass (M(r)) of 140,000), Nap125 (NCK-associated protein with an M(r) of 125,000) and HSPC300. Whereas recombinant WAVE1 is constitutively active, the WAVE1 complex is inactive. We therefore propose that Rac1 and Nck cause dissociation of the WAVE1 complex, which releases active WAVE1-HSPC300 and leads to actin nucleation.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Rac1 signaling can activate the WRC through CYFIP1.
“In particular, the Rac1 signaling can activate the WRC through CYFIP1 (Chen et al., 2010, Eden et al., 2002, Kobayashi et al., 1998, Schenck et al., 2003, Steffen et al., 2004).”
From CYFIP1 Coordinates mRNA Translation and Cytoskeleton Remodeling to Ensure Proper Dendritic Spine Formation (2013) · cites this paper as Eden et al., 2002
Compared with their paralogs, WAVE1, CYFIP2, NCKAP1 and ABI2 are relatively abundant in the brain.
“Compared with their paralogs, WAVE1, CYFIP2, NCKAP1 and ABI2 are relatively abundant in the brain19,20,22 (Fig. 1).”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [19]
WAVE proteins exist as heteropentameric complexes together with regulatory proteins including CYFIP, NCKAP, ABI and BRK1 (specifically NCKAP1/1L, CYFIP1/2, ABI1/2/3, and BRK1).
“WAVE proteins exist as heteropentameric complexes together with regulatory proteins, including CYFIP, NCKAP, ABI and BRK1.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [19]
Several studies have used intact WAVE complexes isolated from the brain or cells.
“In fact, several studies have used intact WAVE complexes isolated from the brain or cells19,20,22,179.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [19]
Cites
p140Sra-1 (specifically Rac1-associated protein) is a novel specific target for Rac1 small GTPase
Kobayashi, K., Kuroda, S., Fukata, M., Nakamura, T., Nagase, T., Nomura, N., Matsuura, Y., Yoshida-Kubomura, N., Iwamatsu, A., & Kaibuchi, K. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.1.291 · Cited by 244 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
AKAP signalling complexes: focal points in space and time
Wong, W., & Scott, J. D. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1527 · Cited by 1,073 · see citing works
Phagocytosis: Receptors, signal integration, and the cytoskeleton
Freeman, S. A., & Grinstein, S. (2014) · Immunological Reviews · doi:10.1111/imr.12212 · Cited by 548 · see citing works
Kunda, P., Craig, G., Dominguez, V., & Baum, B. (2003) · Current Biology · doi:10.1016/j.cub.2003.10.005 · Cited by 341 · see citing works
Schenck, A., Bardoni, B., Langmann, C., Harden, N., Mandel, J.-L., & Giangrande, A. (2003) · Neuron · doi:10.1016/s0896-6273(03)00354-4 · Cited by 316 · see citing works
De Rubeis, S., Pasciuto, E., Li, K. W., Fernández, E., Di Marino, D., Buzzi, A., Ostroff, L. E., Klann, E., Zwartkruis, F. J. T., Komiyama, N. H., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.06.039 · Cited by 296 · see citing works
Chen, E. H., Grote, E., Mohler, W., & Vignery, A. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.03.033 · Cited by 263 · see citing works
Grove, M., Demyanenko, G., Echarri, A., Zipfel, P. A., Quiroz, M. E., Rodriguiz, R. M., Playford, M., Martensen, S. A., Robinson, M. R., Wetsel, W. C., et al. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.24.10905-10922.2004 · Cited by 136 · see citing works
CYFIP family proteins between autism and intellectual disability: links with Fragile X syndrome
Abekhoukh, S., & Bardoni, B. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00081 · Cited by 110 · see citing works
Rakeman, A. S., & Anderson, K. V. (2006) · Development · doi:10.1242/dev.02473 · Cited by 107 · see citing works
Lotto, J., Drissler, S., Cullum, R., Wei, W., Setty, M., Bell, E. M., Boutet, S. C., Nowotschin, S., Kuo, Y.-Y., Garg, V., et al. (2020) · Cell · doi:10.1016/j.cell.2020.09.012 · Cited by 86 · see citing works
Cellular and disease functions of the Prader–Willi Syndrome gene<i>MAGEL2</i>
Tacer, K. F., & Potts, P. R. (2017) · Biochemical Journal · doi:10.1042/bcj20160616 · Cited by 81 · see citing works
An approach for extensibly profiling the molecular states of cellular subpopulations
Loo, L.-H., Lin, H.-J., Steininger, R. J., Wang, Y., Wu, L. F., & Altschuler, S. J. (2009) · Nature Methods · doi:10.1038/nmeth.1375 · Cited by 69 · see citing works
The NESH/Abi-3-based WAVE2 complex is functionally distinct from the Abi-1-based WAVE2 complex
Sekino, S., Kashiwagi, Y., Kanazawa, H., Takada, K., Baba, T., Sato, S., Inoue, H., Kojima, M., & Tani, K. (2015) · Cell Communication and Signaling · doi:10.1186/s12964-015-0119-5 · Cited by 43 · see citing works
Ura, S., Pollitt, A. Y., Veltman, D. M., Morrice, N. A., Machesky, L. M., & Insall, R. H. (2012) · Current Biology · doi:10.1016/j.cub.2012.02.020 · Cited by 50 · see citing works
<scp>RhoA</scp> regulation in space and time
de Seze, J., Gatin, J., & Coppey, M. (2023) · FEBS Letters · doi:10.1002/1873-3468.14578 · Cited by 42 · see citing works
Reduced Complexity Cross Design for Behavioral Genetics
Bryant, C. D., Ferris, M. T., De Villena, F. P. M., Damaj, M. I., Kumar, V., & Mulligan, M. K. (2018) · Molecular-Genetic and Statistical Techniques for Behavioral and Neural Research · doi:10.1016/b978-0-12-804078-2.00008-8 · Cited by 24 · see citing works
The WAVE complex in developmental and adulthood brain disorders
Kim, H.-G., Berdasco, C., Nairn, A. C., & Kim, Y. (2025) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01386-w · Cited by 8 · see citing works
- Authors
- Eden, S., Rohatgi, R., Podtelejnikov, A. V., Mann, M., & Kirschner, M. W.
- Affiliations
- Harvard University (US)
- University of Southern Denmark (DK)
- Corresponding author
- Kirschner, Marc W.
- Venue
- Nature
- Published
- 2002-08
- Volume
- 418
- Issue
- 6899
- Pages
- 790-793
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2089472706
- Cited by
- 835
- References
- 1
- Citations by year
- 2026: 14 · 2025: 15 · 2024: 8 · 2023: 31 · 2022: 30 · 2021: 31 · 2020: 37 · 2019: 22 · 2018: 15 · 2017: 31 · 2016: 24 · 2015: 34 · 2014: 33 · 2013: 43 · 2012: 31
- FWCI
- 20.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- WAVE1, Rac1, Nck, actin nucleation, actin polymerization, WAVE complex, cell motility, protein complex dissociation, adaptor proteins
- MeSH terms
- Actins, Animals, Carrier Proteins, Cattle, Humans, Microfilament Proteins, Protein Binding, Wiskott-Aldrich Syndrome, Signal Transduction, Oncogene Proteins, rac1 GTP-Binding Protein, Macromolecular Substances, Adaptor Proteins, Signal Transducing, Wiskott-Aldrich Syndrome Protein Family
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
