Phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) specifically induces membrane penetration and deformation by Bin/amphiphysin/Rvs (BAR) domains
Open accessAbstract
Cellular proteins containing Bin/amphiphysin/Rvs (BAR) domains play a key role in clathrin-mediated endocytosis. Despite extensive structural and functional studies of BAR domains, it is still unknown how exactly these domains interact with the plasma membrane containing phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)) and whether they function by a universal mechanism or by different mechanisms. Here we report that PtdIns(4,5)P(2) specifically induces partial membrane penetration of the N-terminal amphiphilic α-helix (H(0)) of two representative N-BAR domains from Drosophila amphiphysin (dAmp-BAR) and rat endophilin A1 (EndoA1-BAR). Our quantitative fluorescence imaging analysis shows that PtdIns(4,5)P(2)-dependent membrane penetration of H(0) is important for self-association of membrane-bound dAmp-BAR and EndoA1-BAR and their membrane deformation activity. EndoA1-BAR behaves differently from dAmp-BAR because the former has an additional amphiphilic α-helix that penetrates the membrane in a PtdIns(4,5)P(2)-independent manner. Depletion of PtdIns(4,5)P(2) from the plasma membrane of HEK293 cells abrogated the membrane deforming activity of EndoA1-BAR and dAmp-BAR. Collectively, these studies suggest that the local PtdIns(4,5)P(2) concentration in the plasma membrane may regulate the membrane interaction and deformation by N-BAR domain-containing proteins during clathrin-mediated endocytosis.
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After clathrin recruitment, PI(4,5)P2 facilitates membrane deformation; epsin binds PI(4,5)P2 and inserts an amphipathic helix, and BAR domain proteins also contribute.
“After clathrin recruitment, PI(4,5)P2 facilitates membrane deformation. Epsin binds to PI(4,5)P2, localising epsin to the endocytic site where it inserts an amphipathic helix for membrane deformation [101,102]. Accessory proteins with BAR (domain named after three proteins: Bin, Amphiphysin and Rvs that share the domain) domains, which also bind PI(4,5)P2, also contribute to deformation of the”
From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [103]
The Discussion (page unavailable) says that epsin1’s ENTH helix forms a PI(4,5)P2-binding site, and the paper describes that helix as penetrating the membrane. Figure 7 and the Discussion support PI(4,5)P2-dependent membrane deformation by N-BAR domains. Our copy does not establish the claimed sequence after clathrin recruitment or specifically show that PI(4,5)P2 localises epsin to the endocytic site. (LLM, conf=0.82)
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Localized Biphasic Changes in Phosphatidylinositol-4,5-Bisphosphate at Sites of Phagocytosis
Botelho, R. J., Teruel, M., Dierckman, R., Anderson, R., Wells, A., York, J. D., Meyer, T., & Grinstein, S. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.151.7.1353 · Cited by 539 · cited 1× · see citing works
“1%), local enrichment of PtdIns(4,5)P2 in the plasma membrane has been reported recently (70, 71).”
BackgroundAn inducible translocation strategy to rapidly activate and inhibit small GTPase signaling pathways.
Inoue, T., Heo, W. D., Grimley, J. S., Wandless, T. J., & Meyer, T. (2005) · Nature Methods · doi:10.1038/nmeth763 · Cited by 424 · see citing works
Habermann, B. (2004) · The EMBO Reports · doi:10.1038/sj.embor.7400105 · Cited by 281 · see citing works
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- Garrenton, L. S., Stefan, C. J., McMurray, M. A., Emr, S. D., and Thorner, J. (2010) Pheromone-induced anisotropy in yeast plasma membrane phosphatidylinositol-4,5-bisphosphate distribution is required for MAPK signaling. Proc. Natl. Acad. Sci. U.S.A. 107, 11805-11810 PtdIns(4,5)P 2 and N-BAR Domains
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Endophilin marks and controls a clathrin-independent endocytic pathway
Boucrot, E., Ferreira, A. P. A., Almeida-Souza, L., Debard, S., Vallis, Y., Howard, G., Bertot, L., Sauvonnet, N., & McMahon, H. T. (2015) · Nature · doi:10.1038/nature14067 · Cited by 542 · see citing works
Phosphatidylinositol(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
Cholesterol selectively activates canonical Wnt signalling over non-canonical Wnt signalling
Sheng, R., Kim, H., Lee, H., Xin, Y., Chen, Y., Tian, W., Cui, Y., Choi, J.-C., Doh, J., Han, J.-K., et al. (2014) · Nature Communications · doi:10.1038/ncomms5393 · Cited by 157 · see citing works
Self-citation
- Authors
- Yoon, Y., Zhang, X., & Cho, W.
- Affiliations
- University of Illinois Chicago (US)
- Corresponding author
- Cho, Wonhwa
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2012-10
- Volume
- 287
- Issue
- 41
- Pages
- 34078-34090
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3464517
- OpenAlex
- W2030472411
- Cited by
- 47
- References
- 3
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 6 · 2019: 4 · 2018: 3 · 2017: 3 · 2016: 3 · 2015: 1 · 2014: 12 · 2013: 6
- FWCI
- 3.03
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM 68849, R01GM068849)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
- Keywords
- phosphatidylinositol 4,5-bisphosphate, BAR domain, amphiphysin, endophilin A1, membrane penetration, membrane deformation, clathrin-mediated endocytosis, amphiphilic alpha-helix, protein self-association, plasma membrane, lipid signaling
- MeSH terms
- Acyltransferases, Animals, Cell Membrane, Clathrin, Drosophila melanogaster, Endocytosis, Humans, Nerve Tissue Proteins, Protein Structure, Secondary, Protein Structure, Tertiary, Phosphatidylinositol 4,5-Diphosphate, Drosophila Proteins, Rats, Forkhead Transcription Factors, HEK293 Cells
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