Identification of Two Human WAVE/SCAR Homologues as General Actin Regulatory Molecules Which Associate with the Arp2/3 Complex
Abstract
WAVE/SCAR protein was identified as a protein which has similarity to WASP and N-WASP, especially in its C terminal. Recently, WAVE/SCAR protein has been shown to cooperate with the Arp2/3 complex, a nucleation core for actin polymerization in vitro. However, in spite of its general function, WAVE/SCAR expression is mainly restricted to the brain, suggesting the existence of related molecule(s). We here identified two human WAVE/SCAR homologues, which cover other organs. We named the original WAVE1 and newly identified ones WAVE2 and WAVE3. WAVE2 had a very wide distribution with strong expression in peripheral blood leukocytes and mapped on chromosome Xp11.21, next to the WASP locus. WAVE3 and WAVE1 had similar distributions. WAVE3 was strongly expressed in brain and mapped on chromosome 13q12. WAVE1 was mapped on chromosome 6q21-22. Ectopically expressed WAVE2 and WAVE3 induced actin filament clusters in a similar manner with WAVE1. These actin cluster formations were suppressed by deletion of their C-terminal VPH (verproline homology)/WH2 (WASP homology 2) domain. Further, WAVE2 and WAVE3 associate with the Arp2/3 complex as does WAVE1. Our identification of WAVE homologues suggests that WAVE family proteins have general function for regulating the actin cytoskeleton in many tissues.
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WAVE3 is expressed mainly in the brain, where its levels in interneurons and astrocytes are relatively high.
“WAVE3 is also expressed mainly in the brain16, where its levels in interneurons and astrocytes are relatively high17,18.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [16]
WAVE2 is ubiquitously expressed and is the predominant form in hematopoietic cell lineages, while WAVE1 and WAVE3 expression is limited to neural tissues.
“WAVE2 is ubiquitously expressed and is the predominate form in hematopoietic cell lineages, while WAVE1 and WAVE3 expression is limited to neural tissues [15].”
From HEM1 Actin Immunodysregulatory Disorder: Genotypes, Phenotypes, and Future Directions (2022) · cites this paper as [15]
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Takenawa, T., & Miki, H. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.10.1801 · Cited by 604 · see citing works
Self-citationKim, K. S., Marcogliese, P. C., Yang, J., Callaghan, S. M., Resende, V., Abdel-Messih, E., Marras, C., Visanji, N. P., Huang, J., Schlossmacher, M. G., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1718946115 · Cited by 111 · see citing works
HEM1 Actin Immunodysregulatory Disorder: Genotypes, Phenotypes, and Future Directions
Cook, S., Lenardo, M. J., & Freeman, A. F. (2022) · Journal of Clinical Immunology · doi:10.1007/s10875-022-01327-0 · Cited by 24 · see citing works
The WAVE complex in developmental and adulthood brain disorders
Kim, H.-G., Berdasco, C., Nairn, A. C., & Kim, Y. (2025) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01386-w · Cited by 8 · see citing works
- Authors
- Suetsugu, S., Miki, H., & Takenawa, T.
- Affiliations
- Institute of Medical Science, The University of Tokyo (JP)
- Corresponding author
- Takenawa, Tadaomi
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 1999-06
- Volume
- 260
- Issue
- 1
- Pages
- 296-302
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2021329171
- Cited by
- 246
- References
- 0
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 9 · 2022: 6 · 2021: 6 · 2020: 10 · 2019: 2 · 2018: 3 · 2017: 5 · 2016: 5 · 2015: 3 · 2014: 11 · 2013: 8 · 2012: 9
- FWCI
- 4.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science
- Ministry of Education, Culture, Sports, Science and Technology
- 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 › Microtubule and mitosis dynamics
- Keywords
- WAVE1, WAVE2, WAVE3, Arp2/3 complex, actin polymerization, actin cytoskeleton regulation, WASP family proteins, WH2 domain, gene mapping, peripheral blood leukocytes, brain expression
- MeSH terms
- Actins, Amino Acid Sequence, Animals, Chromosomes, Human, Pair 13, Chromosomes, Human, Pair 6, Cloning, Molecular, Cytoskeletal Proteins, Cytoskeleton, Humans, Microfilament Proteins, Molecular Sequence Data, Tissue Distribution, Databases, Factual, Sequence Homology, Amino Acid, COS Cells, Wiskott-Aldrich Syndrome Protein Family, Actin-Related Protein 2, Actin-Related Protein 3
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