Plasma membrane phosphoinositide organization by protein electrostatics
Abstract
Phosphatidylinositol 4,5-bisphosphate (PIP2), which comprises only about 1% of the phospholipids in the cytoplasmic leaflet of the plasma membrane, is the source of three second messengers, activates many ion channels and enzymes, is involved in both endocytosis and exocytosis, anchors proteins to the membrane through several structured domains and has other roles. How can a single lipid in a fluid bilayer regulate so many distinct physiological processes? Spatial organization might be the key to this. Recent studies suggest that membrane proteins concentrate PIP2 and, in response to local increases in intracellular calcium concentration, release it to interact with other biologically important molecules.
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PI(4,5)P2 is the most abundant phosphoinositide and is enriched in the cytoplasmic leaflet of the plasma membrane, comprising 1-2 mol% of total plasma membrane lipid.
“Of these, PI(4,5)P2 is the most abundant phosphoinositide and is enriched in the cytoplasmic leaflet of the plasma membrane comprising 1–2 mol% of total plasma membrane lipid [3,4].”
From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [3]
PI(4,5)P2 is highly negatively charged and can bind unstructured clusters of basic residues on membrane proteins such as ion channels, receptors and cytoskeletal proteins.
“In addition, PI(4,5)P2 is a highly negatively charged lipid and therefore can bind unstructured clusters of basic residues on numerous membrane proteins (for example, ion channels, receptors and cytoskeletal proteins) [3,11] (see Figure 1C).”
From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [3]
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- Authors
- McLaughlin, S., & Murray, D.
- Affiliations
- Stony Brook University (US)
- Cornell University (US)
- Venue
- Nature
- Published
- 2005-11-30
- Volume
- 438
- Issue
- 7068
- Pages
- 605-611
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2054799935
- Cited by
- 868
- References
- 3
- Citations by year
- 2026: 22 · 2025: 18 · 2024: 16 · 2023: 17 · 2022: 26 · 2021: 30 · 2020: 41 · 2019: 32 · 2018: 29 · 2017: 33 · 2016: 49 · 2015: 61 · 2014: 72 · 2013: 44 · 2012: 51
- FWCI
- 4.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- 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
- Keywords
- phosphatidylinositol 4,5-bisphosphate, plasma membrane, protein-lipid interactions, protein electrostatics, membrane protein clustering, lipid second messengers, calcium signaling, membrane organization, ion channel modulation, membrane protein anchoring
- MeSH terms
- Myristoylated Alanine-Rich C Kinase Substrate, Animals, Calmodulin, Cell Membrane, Membrane Proteins, Phosphatidylinositols, Intracellular Signaling Peptides and Proteins, Static Electricity
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