The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Abi, Sra1, and Kette Control the Stability and Localization of SCAR/WAVE to Regulate the Formation of Actin-Based Protrusions
Open accessAbstract
Background In animal cells, GTPase signaling pathways are thought to generate cellular protrusions by modulating the activity of downstream actin-regulatory proteins. Although the molecular events linking activation of a GTPase to the formation of an actin-based process with a characteristic morphology are incompletely understood, Rac-GTP is thought to promote the activation of SCAR/WAVE, whereas Cdc42 is thought to initiate the formation of filopodia through WASP. SCAR and WASP then activate the Arp2/3 complex to nucleate the formation of new actin filaments, which through polymerization exert a protrusive force on the membrane. Results Using RNAi to screen for genes regulating cell form in an adherent Drosophila cell line, we identified a set of genes, including Abi/E3B1, that are absolutely required for the formation of dynamic protrusions. These genes delineate a pathway from Cdc42 and Rac to SCAR and the Arp2/3 complex. Efforts to place Abi in this signaling hierarchy revealed that Abi and two components of a recently identified SCAR complex, Sra1 (p140/PIR121/CYFIP) and Kette (Nap1/Hem), protect SCAR from proteasome-mediated degradation and are critical for SCAR localization and for the generation of Arp2/3-dependent protrusions. Conclusions In Drosophila cells, SCAR is regulated by Abi, Kette, and Sra1, components of a conserved regulatory SCAR complex. By controlling the stability, localization, and function of SCAR, these proteins may help to ensure that Arp2/3 activation and the generation of actin-based protrusions remain strictly dependant on local GTPase signaling.
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“Indeed, it is reported that reduction of Cyfip1 or fly Hspc300 affects the level of the other components of the WRC (Kunda et al., 2003; Schenck et al., 2004; Abekhoukh and Bardoni, 2014; Gautier et al., 2011; Qurashi et al., 2007; De Rubeis et al., 2013).”
From New insights into the regulatory function of CYFIP1 in the context of WAVE- and FMRP-containing complexes (2017) · cites this paper as Kunda et al., 2003
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Metadata
- Authors
- Kunda, P., Craig, G., Dominguez, V., & Baum, B.
- Affiliations
- University College London (GB)
- Corresponding author
- Baum, Buzz
- ORCID
- Baum, Buzz
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2003-10
- Volume
- 13
- Issue
- 21
- Pages
- 1867-1875
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W2054821269
- Cited by
- 341
- References
- 35
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 11 · 2023: 8 · 2022: 10 · 2021: 12 · 2020: 9 · 2019: 11 · 2018: 15 · 2017: 13 · 2016: 13 · 2015: 12 · 2014: 12 · 2013: 21 · 2012: 10
- FWCI
- 7.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 3577 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Cancer Research UK
- Ludwig Institute for Cancer Research
- Royal Society
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- 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 transport and secretion
- Keywords
- SCAR/WAVE complex, ABI, SR-A1, Arp2/3 complex, actin-based protrusions, filopodia, Cdc42, Rac, GTPase signaling, proteasomal degradation, protein localization, Drosophila cells, cell shape regulation, wasps
- MeSH terms
- Actins, Animals, Carrier Proteins, Cells, Cultured, Drosophila, Fluorescent Antibody Technique, Microfilament Proteins, Pseudopodia, Blotting, Western, Signal Transduction, Drosophila Proteins, RNA Interference, Adaptor Proteins, Signal Transducing, Wiskott-Aldrich Syndrome Protein Family
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