Segregation of PIP2 and PIP3 into distinct nanoscale regions within the plasma membrane
Open accessAbstract
Summary: PIP2 and PIP3 are implicated in a wide variety of cellular signaling pathways at the plasma membrane. We have used STORM imaging to localize clusters of PIP2 and PIP3 to distinct nanoscale regions within the plasma membrane of PC12 cells. With anti-phospholipid antibodies directly conjugated with AlexaFluor 647, we found that PIP2 clusters in membrane domains of 64.5±27.558 nm, while PIP3 clusters had a size of 125.6±22.408 nm. With two color direct STORM imaging we show that >99% of phospholipid clusters have only one or other phospholipid present. These results indicate that lipid nano-domains can be readily identified using super-resolution imaging techniques, and that the lipid composition and size of clusters is tightly regulated.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
PI(4,5)P2 forms dynamic clusters at nanoscale; STED microscopy on PC12 cell plasma membranes found clusters of ∼65-73 nm.
“Using super-resolution stimulated-emission depletion (STED) microscopy on the plasma membranes of PC12 cells, PI(4,5)P2 was found in clusters of ∼65–73 nm in size [110,126].”
From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [126]
The Results and Discussion (Fig. 1 and accompanying text) report PIP2 clusters of about 64–65 nm in PC12 cell plasma membranes, but this paper used dSTORM, not STED microscopy. The same section cites a separate STED study for the approximately 73 nm figure. The cited sentence does not attribute cluster dynamics to this source. (LLM, conf=0.90)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
No references could be resolved yet.
Research works printed but not linked: 26
- Brown D. A. Rose J. K. (1992). Sorting of GPI-anchored proteins to glycolipid-enriched membrane subdomains during transport to the apical cell surface. Cell 68, 533– 544 10.1016/0092-8674(92)90189-J 1531449 · DOI · Paper page
- Corbin J. A. Dirkx R. A. Falke J. J. (2004). GRP1 pleckstrin homology domain: activation parameters and novel search mechanism for rare target lipid. Biochemistry 43, 16161– 16173 10.1021/bi049017a 15610010 PMC3625374 · DOI
- Di Paolo G. De Camilli P. (2006). Phosphoinositides in cell regulation and membrane dynamics. Nature 443, 651– 657 10.1038/nature05185 17035995 · DOI · Paper page
- Goebbels S. Oltrogge J. H. Kemper R. Heilmann I. Bormuth I. Wolfer S. Wichert S. P. Möbius W. Liu X. Lappe-Siefke C. (2010). Elevated phosphatidylinositol 3,4,5-trisphosphate in glia triggers cell-autonomous membrane wrapping and myelination. J. Neurosci. 30, 8953– 8964 10.1523/JNEUROSCI.0219-10.2010 20592216 PMC6632897 · DOI
- Gustafsson M. G. Shao L. Carlton P. M. Wang C. J. Golubovskaya I. N. Cande W. Z. Agard D. A. Sedat J. W. (2008). Three-dimensional resolution doubling in wide-field fluorescence microscopy by structured illumination. Biophys. J. 94, 4957– 4970 10.1529/biophysj.107.120345 18326650 PMC2397368 · DOI
- Harris L. J. Skaletsky E. McPherson A. (1995). Crystallization of intact monoclonal antibodies. Proteins 23, 285– 289 10.1002/prot.340230218 8592710 · DOI
- Hein B. Willig K. I. Hell S. W. (2008). Stimulated emission depletion (STED) nanoscopy of a fluorescent protein-labeled organelle inside a living cell. Proc. Natl. Acad. Sci. USA 105, 14271– 14276 10.1073/pnas.0807705105 18796604 PMC2538451 · DOI
- Huang B. Babcock H. Zhuang X. (2010). Breaking the diffraction barrier: super-resolution imaging of cells. Cell 143, 1047– 1058 10.1016/j.cell.2010.12.002 21168201 PMC3272504 · DOI
- Insall R. H. Weiner O. D. (2001). PIP3, PIP2, and cell movement–similar messages, different meanings? Dev. Cell 1, 743– 747 10.1016/S1534-5807(01)00086-7 11740936 PMC2819114 · DOI
- Krauß M. Haucke V. (2007). Phosphoinositides: regulators of membrane traffic and protein function. FEBS Lett. 581, 2105– 2111 10.1016/j.febslet.2007.01.089 17316616 · DOI
- Lee A. G. Birdsall N. J. Metcalfe J. C. Toon P. A. Warren G. B. (1974). Clusters in lipid bilayers and the interpretation of thermal effects in biological membranes. Biochemistry 13, 3699– 3705 10.1021/bi00715a013 4368511 · DOI
- Leloup L. Shao H. Bae Y. H. Deasy B. Stolz D. Roy P. Wells A. (2010). m-Calpain activation is regulated by its membrane localization and by its binding to phosphatidylinositol 4,5-bisphosphate. J. Biol. Chem. 285, 33549– 33566 10.1074/jbc.M110.123604 20729206 PMC2963356 · DOI
- Maffucci T. Raimondi C. Abu-Hayyeh S. Dominguez V. Sala G. Zachary I. Falasca M. (2009). A phosphoinositide 3-kinase/phospholipase Cgamma1 pathway regulates fibroblast growth factor-induced capillary tube formation. PLoS ONE 4, e8285 10.1371/journal.pone.0008285 20011604 PMC2788267 · DOI
- Manley S. Gillette J. M. Patterson G. H. Shroff H. Hess H. F. Betzig E. Lippincott-Schwartz J. (2008). High-density mapping of single-molecule trajectories with photoactivated localization microscopy. Nat. Methods 5, 155– 157 10.1038/nmeth.1176 18193054 · DOI
- McLaughlin S. Murray D. (2005). Plasma membrane phosphoinositide organization by protein electrostatics. Nature 438, 605– 611 10.1038/nature04398 16319880 · DOI · Paper page
- McLaughlin S. Wang J. Gambhir A. Murray D. (2002). PIP(2) and proteins: interactions, organization, and information flow. Annu. Rev. Biophys. Biomol. Struct. 31, 151– 175 10.1146/annurev.biophys.31.082901.134259 11988466 · DOI · Paper page
- Ménager C. Arimura N. Fukata Y. Kaibuchi K. (2004). PIP3 is involved in neuronal polarization and axon formation. J. Neurochem. 89, 109– 118 10.1046/j.1471-4159.2004.02302.x 15030394 · DOI
- Miao B. Skidan I. Yang J. You Z. Fu X. Famulok M. Schaffhausen B. Torchilin V. Yuan J. Degterev A. (2011). Inhibition of cell migration by PITENINs: the role of ARF6. Oncogene [Epub ahead of print] 10.1038/onc.2011.593 PMC3310973 22179837 · DOI
- Pike L. J. (2006). Rafts defined: a report on the Keystone Symposium on Lipid Rafts and Cell Function. J. Lipid Res. 47, 1597– 1598 10.1194/jlr.E600002-JLR200 16645198 · DOI
- Pike L. J. (2009). The challenge of lipid rafts. J. Lipid Res. 50 Suppl, S323– S328 10.1194/jlr.R800040-JLR200 18955730 PMC2674732 · DOI
- Rust M. J. Bates M. Zhuang X. (2006). Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM). Nat. Methods 3, 793– 796 10.1038/nmeth929 16896339 PMC2700296 · DOI
- Sieber J. J. Willig K. I. Kutzner C. Gerding-Reimers C. Harke B. Donnert G. Rammner B. Eggeling C. Hell S. W. Grubmüller H. (2007). Anatomy and dynamics of a supramolecular membrane protein cluster. Science 317, 1072– 1076 10.1126/science.1141727 17717182 · DOI
- Singer S. J. Nicolson G. L. (1972). The fluid mosaic model of the structure of cell membranes. Science 175, 720– 731 10.1126/science.175.4023.720 4333397 · DOI
- van den Bogaart G. Meyenberg K. Risselada H. J. Amin H. Willig K. I. Hubrich B. E. Dier M. Hell S. W. Grubmüller H. Diederichsen U. (2011). Membrane protein sequestering by ionic protein-lipid interactions. Nature 479, 552– 555 10.1038/nature10545 22020284 PMC3409895 · DOI · Paper page
- Vanhaesebroeck B. Leevers S. J. Ahmadi K. Timms J. Katso R. Driscoll P. C. Woscholski R. Parker P. J. Waterfield M. D. (2001). Synthesis and function of 3-phosphorylated inositol lipids. Annu. Rev. Biochem. 70, 535– 602 10.1146/annurev.biochem.70.1.535 11395417 · DOI · Paper page
- Wang Y. H. Collins A. Guo L. Smith-Dupont K. B. Gai F. Svitkina T. Janmey P. A. (2012). Divalent cation-induced cluster formation by polyphosphoinositides in model membranes. J. Am. Chem. Soc. 134, 3387– 3395 10.1021/ja208640t 22280226 PMC3445022 · DOI
Cited by
Sorted by citations
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
Spoiled for Choice: Diverse Endocytic Pathways Function at the Cell Surface
Thottacherry, J. J., Sathe, M., Prabhakara, C., & Mayor, S. (2019) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100617-062710 · Cited by 122 · see citing works
PH domain-mediated autoinhibition and oncogenic activation of Akt
Bae, H., Viennet, T., Park, E., Chu, N., Salguero, A., Eck, M. J., Arthanari, H., & Cole, P. A. (2022) · eLife · doi:10.7554/elife.80148 · Cited by 31 · see citing works
- Authors
- Wang, J., & Richards, D. A.
- Affiliations
- Cincinnati Children's Hospital Medical Center (US)
- Corresponding author
- Wang, Jie
- Richards, David A.
- Venue
- Biology Open
- Publisher
- The Company of Biologists
- Published
- 2012-07-10
- Volume
- 1
- Issue
- 9
- Pages
- 857-862
- ISSN
- 2046-6390 (ISSN-L)
- PMC
- PMC3507238
- OpenAlex
- W2130826825
- Cited by
- 146
- References
- 0
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 5 · 2023: 13 · 2022: 15 · 2021: 12 · 2020: 20 · 2019: 15 · 2018: 15 · 2017: 11 · 2016: 6 · 2015: 9 · 2014: 11 · 2013: 5
- FWCI
- 3.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Biology Open (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS054750)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Keywords
- phosphatidylinositol 4,5-bisphosphate, phosphatidylinositol 3,4,5-trisphosphate, lipid rafts, plasma membrane, PC12 cells, antiphospholipid antibodies
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
