Cited by 604Cellular Mechanics and InteractionsProtein Kinase Regulation and GTPase SignalingAxon Guidance and Neuronal Signaling

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WASP and WAVE family proteins: key molecules for rapid rearrangement of cortical actin filaments and cell mov

Takenawa, Tadaomi, Miki, Hiroaki·2001·Journal of Cell Science

DOI 10.1242/jcs.114.10.1801

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Abstract

Reorganization of cortical actin filaments plays critical roles in cell movement and pattern formation. Recently, the WASP and WAVE family proteins WASP and N-WASP, and WAVE1, WAVE2 and WAVE3 have been shown to regulate cortical actin filament reorganization in response to extracellular stimuli. These proteins each have a verprolin-homology (V) domain, cofilin-homology (C) domain and an acidic (A) region at the C-terminus, through which they activate the Arp2/3 complex, leading to rapid actin polymerization. N-WASP is usually present as an inactive form in which the VCA region is masked. Cooperative binding of Cdc42 and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) exposes the VCA region, activating N-WASP. In addition to this activation mechanism, WISH also activates N-WASP independently of Cdc42 and PtdIns(4,5)P2, by binding to the proline-rich region of N-WASP. N-WASP activation induces formation of filopodia in vivo. In contrast, the ubiquitously expressed form of WAVE2 is activated downstream of Rac, leading to formation of lamellipodia. In this case, IRSp53 transmits a signal from Rac to WAVE2 through formation of a ternary Rac-IRSp53-WAVE2 complex. Thus, N-WASP, which is activated downstream of Cdc42 or independently by WISH, induces formation of filopodia and WAVE2, which is activated via IRSp53 downstream of Rac, induces formation of lamellipodia.

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Authors: Takenawa, T., & Miki, H.
Affiliations: Institute of Medical Science, The University of Tokyo (JP)
ORCID: Miki, Hiroaki
Venue: Journal of Cell Science
Publisher: The Company of Biologists
Published: 2001-05-15
Volume: 114
Issue: 10
Pages: 1801-1809
ISSN: 0021-9533 (ISSN-L)
1477-9137
DOI: 10.1242/jcs.114.10.1801
OpenAlex: W1960862471
Cited by: 604
References: 77
Citations by year: 2026: 7 · 2025: 6 · 2024: 9 · 2023: 5 · 2022: 6 · 2021: 10 · 2020: 14 · 2019: 9 · 2018: 9 · 2017: 15 · 2016: 15 · 2015: 14 · 2014: 16 · 2013: 25 · 2012: 27
FWCI: 4.03
Type: journal article
Language: en
Open access: closed
Licence: www.biologists.com/user-licence-1-1/ (vor)
Locations: Journal of Cell Science (publishedVersion)
PubMed (publishedVersion)
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 › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
Keywords: wasps, N-WASP, cell motility, Arp2/3 complex, actin polymerization, Cdc42, phosphatidylinositol 4,5-bisphosphate, wishes, IRSp53, Rac, filopodia, lamellipodia
MeSH terms: Animals, Cell Movement, Eukaryotic Cells, Humans, Microfilament Proteins, Actin Cytoskeleton, Proteins, Signal Transduction, Wiskott-Aldrich Syndrome Protein Family, Wiskott-Aldrich Syndrome Protein

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WASP and WAVE family proteins: key molecules for rapid rearrangement of cortical actin filaments and cell mov

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