Lamellipodial Versus Filopodial Mode of the Actin Nanomachinery
Open accessAbstract
Understanding how a particular cell type expresses the lamellipodial or filopodial form of the actin machinery is essential to understanding a cell's functional interactions. To determine how a cell "chooses" among these alternative modes of "molecular hardware," we tested the role of key proteins that affect actin filament barbed ends. Depletion of capping protein (CP) by short hairpin RNA (shRNA) caused loss of lamellipodia and explosive formation of filopodia. The knockdown phenotype was rescued by a CP mutant refractory to shRNA, but not by another barbed-end capper, gelsolin, demonstrating that the phenotype was specific for CP. In Ena/VASP deficient cells, CP depletion resulted in ruffling instead of filopodia. We propose a model for selection of lamellipodial versus filopodial organization in which CP is a negative regulator of filopodia formation and Ena/VASP has recruiting/activating functions downstream of actin filament elongation in addition to its previously suggested anticapping and antibranching activities.
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Capping proteins control the growth of actin filaments in lamellipodia, resulting in filopodia formation and a reduction in lamellipodia.
“These capping proteins control the growth of actin filaments in lamellipodia, resulting in filopodia formation and a reduction in lamellipodia.40”
From SHANK3 mutations identified in autism lead to modification of dendritic spine morphology via an actin-dependent mechanism (2012) · cites this paper as [40]
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- Authors
- Mejillano, M. R., Kojima, S.-I., Applewhite, D. A., Gertler, F. B., Svitkina, T. M., & Borisy, G. G.
- Affiliations
- Northwestern University (US)
- Massachusetts Institute of Technology (US)
- University of Pennsylvania (US)
- Corresponding author
- Borisy, Gary G.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2004-08
- Volume
- 118
- Issue
- 3
- Pages
- 363-373
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2014906153
- Cited by
- 420
- References
- 56
- Citations by year
- 2026: 12 · 2025: 8 · 2024: 7 · 2023: 8 · 2022: 10 · 2021: 19 · 2020: 17 · 2019: 20 · 2018: 13 · 2017: 11 · 2016: 21 · 2015: 14 · 2014: 21 · 2013: 18 · 2012: 25
- FWCI
- 10.80
- 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, 3272 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
- Cell (publishedVersion)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- National Institute of General Medical Sciences (GM-58801, R01GM062431, R01GM058801, GM62431)
- 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
- lamellipodia, filopodia, actin cytoskeleton, capping protein, Ena/VASP, gelsolin, barbed end capping, actin filament barbed end, cell motility, shRNA knockdown
- MeSH terms
- Vasodilator-Stimulated Phosphoprotein, Actins, Animals, Carrier Proteins, Cytoskeletal Proteins, Kinetics, Microfilament Proteins, Microscopy, Electron, Phosphoproteins, Pseudopodia, Cell Adhesion Molecules, Actin Depolymerizing Factors, Destrin, Mice
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