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Cited by 254Protein Kinase Regulation and GTPase SignalingSphingolipid Metabolism and SignalingLipid metabolism and biosynthesis

Understanding phosphoinositides: rare, dynamic, and essential membrane phospholipids

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Dickson, Eamonn J., Hille, Bertil·2019·Biochemical Journal
DOI 10.1042/bcj20180022PMC PMC6342281
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Abstract

Polyphosphoinositides (PPIs) are essential phospholipids located in the cytoplasmic leaflet of eukaryotic cell membranes. Despite contributing only a small fraction to the bulk of cellular phospholipids, they make remarkable contributions to practically all aspects of a cell's life and death. They do so by recruiting cytoplasmic proteins/effectors or by interacting with cytoplasmic domains of membrane proteins at the membrane–cytoplasm interface to organize and mold organelle identity. The present study summarizes aspects of our current understanding concerning the metabolism, manipulation, measurement, and intimate roles these lipids play in regulating membrane homeostasis and vital cell signaling reactions in health and disease.

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  • IP3 mobilises Ca2+ from ER stores.

    “Phospholipase C (PLC) leads to the generation of two second messengers, inositol(1,4,5)trisphosphate (I(1,4,5)P3), known trigger for mobilising Ca2+ from endoplasmic reticulum (ER) stores and diacylglycerol (DAG), an activator for protein kinase C (PKC).”

    From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [16]

    The “Physiological roles of phosphoinositides” section says PLC produces IP3 and DAG and that IP3 releases calcium from intracellular stores. It does not identify those stores specifically as the endoplasmic reticulum, so the ER-specific part of the claim is not established by our copy. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • PI(4,5)P2 is a substrate for PLC and PI3K.

    “PI(4,5)P2 is a substrate for two signalling pathways.”

    From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [16]

  • PLC hydrolysis of PI(4,5)P2 generates IP3 and DAG.

    “Phospholipase C (PLC) leads to the generation of two second messengers, inositol(1,4,5)trisphosphate (I(1,4,5)P3), known trigger for mobilising Ca2+ from endoplasmic reticulum (ER) stores and diacylglycerol (DAG), an activator for protein kinase C (PKC).”

    From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [16]

  • DAG activates PKC.

    “Phospholipase C (PLC) leads to the generation of two second messengers, inositol(1,4,5)trisphosphate (I(1,4,5)P3), known trigger for mobilising Ca2+ from endoplasmic reticulum (ER) stores and diacylglycerol (DAG), an activator for protein kinase C (PKC).”

    From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [16]

  • PI3K generates PI(3,4,5)P3, a lipid with wide-ranging functions.

    “The second pathway is phosphoinositide-3-kinase (PI3K) to make PI(3,4,5)P3, a lipid with wide-ranging functions.”

    From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [16]

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References 185 · Cited by 254

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Authors
Dickson, E. J., & Hille, B.
Affiliations
  • University of California, Davis (US)
  • University of Washington (US)
Corresponding author
Dickson, Eamonn J.
ORCID
Venue
Biochemical Journal
Publisher
Portland Press Ltd.
Published
2019-01-07
Volume
476
Issue
1
Pages
1-23
ISSN
  • 0264-6021 (ISSN-L)
  • 1470-8728
DOI
10.1042/bcj20180022
PMC
PMC6342281
OpenAlex
W2908733085
Cited by
254
References
185
Citations by year
2026: 29 · 2025: 30 · 2024: 32 · 2023: 36 · 2022: 39 · 2021: 35 · 2020: 31 · 2019: 22
FWCI
2.80
Type
journal article
Language
en
Open access
Locations
  • Biochemical Journal (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Institute of General Medical Sciences (R01GM127513)
  • National Institute of Neurological Disorders and Stroke (R37NS008174)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Keywords
polyphosphoinositides, phosphoinositides, membrane phospholipids, membrane homeostasis, signal transduction, lipid metabolism, lipid measurement, cell death
MeSH terms
Animals, Cell Membrane, Humans, Membrane Proteins, Phosphatidylinositols, Signal Transduction

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 ›

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