PtdIns(3,4,5)P 3 is a regulator of myosin-X localization and filopodia formation
Abstract
Phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P₃] is a key regulator of cell signaling that acts by recruiting proteins to the cell membrane, such as at the leading edge during cell migration. Here, we show that PtdIns (3,4,5)P₃ plays a central role in filopodia formation via the binding of myosin-X (Myo10), a potent promoter of filopodia. We found that the second pleckstrin homology domain (Myo10-PH2) of Myo10 specifically binds to PtdIns(3,4,5)P₃, and that disruption of this binding led to impairment of filopodia and partial re-localization of Myo10 to microtubule-associated Rab7-positive endosomal vesicles. Given that the localization of Myo10 was dynamically restored to filopodia upon reinstatement of PtdIns(3,4,5)P₃-binding, our results indicate that PtdIns(3,4,5)P₃ binding to the Myo10-PH2 domain is involved in Myo10 trafficking and regulation of filopodia dynamics.
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Interactions of proteins with PI(3,4,5)P3 and PI(3,4)P2 not mediated by PH domains or related modules have been described, for example specific isoforms of myosin motor proteins.
“Interactions of proteins with these lipids, not mediated by the PH-domains or related modules, have also been described; one example are specific isoforms of the myosin motor proteins [82,83].”
From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [83]
Cites
Shaner, N. C., Campbell, R. E., Steinbach, P. A., Giepmans, B. N. G., Palmer, A. E., & Tsien, R. Y. (2004) · Nature Biotechnology · doi:10.1038/nbt1037 · Cited by 4,619 · see citing works
Park, W. S., Do Heo, W., Whalen, J. H., O'Rourke, N. A., Bryan, H. M., Meyer, T., & Teruel, M. N. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.04.008 · Cited by 167 · see citing works
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Phosphoinositides in Control of Membrane Dynamics
Schink, K. O., Tan, K.-W., & Stenmark, H. (2016) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-111315-125349 · Cited by 283 · see citing works
Jacquemet, G., Baghirov, H., Georgiadou, M., Sihto, H., Peuhu, E., Cettour-Janet, P., He, T., Perälä, M., Kronqvist, P., Joensuu, H., et al. (2016) · Nature Communications · doi:10.1038/ncomms13297 · Cited by 186 · see citing works
Self-citationPhosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane
Katan, M., & Cockcroft, S. (2020) · Essays in Biochemistry · doi:10.1042/ebc20200041 · Cited by 176 · see citing works
- Authors
- Plantard, L., Arjonen, A., Lock, J. G., Nurani, G., Ivaska, J., & Strömblad, S.
- Affiliations
- Karolinska Institutet (SE)
- University of Turku (FI)
- Corresponding author
- Strömblad, Staffan
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2010-10-15
- Volume
- 123
- Issue
- 20
- Pages
- 3525-3534
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W2168014973
- Cited by
- 84
- References
- 2
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 6 · 2022: 4 · 2021: 5 · 2020: 9 · 2019: 6 · 2018: 4 · 2017: 2 · 2016: 9 · 2015: 7 · 2014: 4 · 2013: 6 · 2012: 9
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- phosphatidylinositol 3,4,5-trisphosphate, myosin X, Myo10, filopodia formation, pleckstrin homology domain, protein localization, phosphoinositide signaling, cell migration
- MeSH terms
- Animals, Chlorocebus aethiops, HeLa Cells, Humans, Myosins, Protein Binding, Pseudopodia, Endosomes, Protein Structure, Tertiary, Phosphatidylinositol Phosphates, COS Cells, Immunoprecipitation
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