Cited by 347Cellular Mechanics and InteractionsProtein Kinase Regulation and GTPase SignalingCellular transport and secretion

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Abi, Sra1, and Kette Control the Stability and Localization of SCAR/WAVE to Regulate the Formation of Actin-Based Protrusions

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Kunda, Patricia, Craig, Gavin, Dominguez, Veronica, Baum, Buzz·2003·Current Biology

DOI 10.1016/j.cub.2003.10.005

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Abstract

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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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)
DOI: 10.1016/j.cub.2003.10.005
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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Abi, Sra1, and Kette Control the Stability and Localization of SCAR/WAVE to Regulate the Formation of Actin-Based Protrusions

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