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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Reduction of Cyfip1 or fly Hspc300 affects the level of the other components of the WRC.
“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
The Results report that silencing fly Sra1 or HSPC300 reduced the level of SCAR, another WRC component. This supports the claim for SCAR, but the paper does not establish that levels of the other WRC components generally are affected, or test reduction of mammalian CYFIP1. (LLM, conf=0.84)
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- 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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