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Cited by 617Cellular transport and secretionLipid Membrane Structure and BehaviorExtracellular vesicles in disease

Membrane protein sequestering by ionic protein–lipid interactions

Open access
van den Bogaart, Geert, Meyenberg, Karsten, Risselada, H. Jelger, Amin, Hayder, Willig, Katrin I., Hubrich, Barbara E., Dier, Markus, Hell, Stefan W. +3 more·2011·Nature
DOI 10.1038/nature10545PMC PMC3409895
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Abstract

Neuronal exocytosis is catalysed by the SNAP receptor protein syntaxin-1A, which is clustered in the plasma membrane at sites where synaptic vesicles undergo exocytosis. However, how syntaxin-1A is sequestered is unknown. Here we show that syntaxin clustering is mediated by electrostatic interactions with the strongly anionic lipid phosphatidylinositol-4,5-bisphosphate (PIP2). Using super-resolution stimulated-emission depletion microscopy on the plasma membranes of PC12 cells, we found that PIP2 is the dominant inner-leaflet lipid in microdomains about 73 nanometres in size. This high accumulation of PIP2 was required for syntaxin-1A sequestering, as destruction of PIP2 by the phosphatase synaptojanin-1 reduced syntaxin-1A clustering. Furthermore, co-reconstitution of PIP2 and the carboxy-terminal part of syntaxin-1A in artificial giant unilamellar vesicles resulted in segregation of PIP2 and syntaxin-1A into distinct domains even when cholesterol was absent. Our results demonstrate that electrostatic protein-lipid interactions can result in the formation of microdomains independently of cholesterol or lipid phases.

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  • Several PI(4,5)P2-binding proteins have important functions in SNARE complex assembly, including synaptotagmin-1, Munc13-1, CAPS, and syntaxin-1.

    “Several PI(4,5P)2-binding proteins have been identified with important functions in SNARE complex assembly, including C2-domain-containing proteins, synaptotagmin-1 and Munc13-1 [109], PH- and C2-domain-containing protein CAPS (Ca2+-dependent activator protein for secretion), and syntaxin-1 [110].”

    From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [110]

    The paper’s main text (indexed under Abstract; page unavailable) identifies CAPS among proteins whose interactions with PIP2 probably mediate docking and fusion. It also reports that syntaxin-1A binds PIP2 and says its accumulation may facilitate SNARE interactions. It does not establish that CAPS has a role specifically in SNARE complex assembly; synaptotagmin-1 and Munc13-1 are attached to a different citation in the citing sentence. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • 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 [110]

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Research works printed but not linked: 28

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Authors
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., & Jahn, R.
Affiliations
  • University of Göttingen (DE)
  • Max Planck Institute for Biophysical Chemistry (DE)
Corresponding author
Jahn, Reinhard
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2011-10-23
Volume
479
Issue
7374
Pages
552-555
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature10545
PMC
PMC3409895
OpenAlex
W2138936877
Cited by
617
References
1
Citations by year
2026: 10 · 2025: 24 · 2024: 17 · 2023: 34 · 2022: 39 · 2021: 41 · 2020: 38 · 2019: 35 · 2018: 38 · 2017: 78 · 2016: 50 · 2015: 64 · 2014: 59 · 2013: 52 · 2012: 37
FWCI
22.87
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • Max Planck Digital Library (submittedVersion, other-oa)
  • GRO (submittedVersion, cc-by)
  • MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
  • OPUS (Augsburg University) (submittedVersion)
Funders
  • Deutsche Forschungsgemeinschaft (SFB803)
  • National Institutes of Health (GM072694)
  • National Institute of General Medical Sciences (P01GM072694)
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 › Molecular Biology › Extracellular vesicles in disease
Keywords
syntaxin 1A, phosphatidylinositol 4,5-bisphosphate, lipid rafts, synaptic vesicle exocytosis, SNARE proteins, SYNJ1, plasma membrane organization, giant unilamellar vesicles, PC12 cells
MeSH terms
Animals, Cholesterol, Nerve Tissue Proteins, Phosphoric Monoester Hydrolases, Protein Binding, PC12 Cells, Microscopy, Confocal, Phosphatidylinositol 4,5-Diphosphate, Membrane Microdomains, Syntaxin 1, Rats, Unilamellar Liposomes, Static Electricity, Molecular Dynamics Simulation

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