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Cited by 24Protein Kinase Regulation and GTPase SignalingCellular Mechanics and InteractionsCellular transport and secretion

Arf GTPase activates the WAVE regulatory complex through a distinct binding site

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Yang, Sheng, Tang, Yubo, Liu, Yijun, Brown, Abbigale J., Schaks, Matthias, Ding, Bojian, Kramer, Daniel A., Mietkowska, Magdalena +7 more·2022·Science Advances
DOI 10.1126/sciadv.add1412PMC PMC9750158
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Abstract

Cross-talk between Rho- and Arf-family guanosine triphosphatases (GTPases) plays an important role in linking the actin cytoskeleton to membrane protrusions, organelle morphology, and vesicle trafficking. The central actin regulator, WAVE regulatory complex (WRC), integrates Rac1 (a Rho-family GTPase) and Arf signaling to promote Arp2/3-mediated actin polymerization in many processes, but how WRC senses Arf signaling is unknown. Here, we have reconstituted a direct interaction between Arf and WRC. This interaction is greatly enhanced by Rac1 binding to the D site of WRC. Arf1 binds to a previously unidentified, conserved surface on the Sra1 subunit of WRC, which, in turn, drives WRC activation using a mechanism distinct from that of Rac1. Mutating the Arf binding site abolishes Arf1-WRC interaction, disrupts Arf1-mediated WRC activation, and impairs lamellipodia formation and cell migration. This work uncovers a new mechanism underlying WRC activation and provides a mechanistic foundation for studying how WRC-mediated actin polymerization links Arf and Rac signaling in cells.

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  • ARF1 directly binds to a distinct site on CYFIP1, which is greatly enhanced by RAC1 binding, and thereby activates the WAVE complex.

    “In addition, ARF1 directly binds to a distinct site on CYFIP1, which is greatly enhanced by RAC1 binding, and thereby activates the WAVE complex34,35.”

    From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [34]

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Authors
Yang, S., Tang, Y., Liu, Y., Brown, A. J., Schaks, M., Ding, B., Kramer, D. A., Mietkowska, M., Ding, L., Alekhina, O., Billadeau, D. D., Chowdhury, S., Wang, J., Rottner, K., & Chen, B.
Affiliations
  • Iowa State University (US)
  • Helmholtz Centre for Infection Research (DE)
  • Stony Brook University (US)
  • Division of Molecular Cell Biology, Zoological Institute, Technische Universität Braunschweig, Spielmannstrasse 7, 38106 Braunschweig, Germany.
  • Mayo Clinic (US)
  • Centre for Cellular and Molecular Biology (IN)
  • University of Pittsburgh (US)
Corresponding author
  • Tang, Yubo
  • Liu, Yijun
  • Rottner, Klemens
  • Chen, Baoyu
ORCID
Venue
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Published
2022-12-16
Volume
8
Issue
50
Pages
eadd1412-eadd1412
ISSN
2375-2548 (ISSN-L)
DOI
10.1126/sciadv.add1412
PMC
PMC9750158
OpenAlex
W4311456707
Cited by
24
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0
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journal article
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en
Open access
Licence
cc-by-nc
Locations
  • Science Advances (publishedVersion, cc-by-nc)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Iowa State University Digital Repository (Iowa State University) (submittedVersion, cc-by-nc)
Funders
  • National Science Foundation (1955260)
  • Roy J. Carver Charitable Trust
  • University of Texas Southwestern Medical Center
  • Drexel University
  • Iowa State University
  • Deutsche Forschungsgemeinschaft (GRK2223, RO2414/8-1)
  • Stony Brook University
  • National Institutes of Health
  • National Institute of General Medical Sciences (R01GM079383, R01GM147673, R35GM128786)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK107733)
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
Arf GTPases, Arf1, WAVE regulatory complex, SR-A1, Rac1, Arp2/3 complex, actin polymerization, lamellipodia formation, cell migration, actin cytoskeleton regulation

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 ›

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