PIP2and Proteins: Interactions, Organization, and Information Flow
Abstract
We review the physical properties of phosphatidylinositol 4,5-bisphosphate (PIP2) that determine both its specific interactions with protein domains of known structure and its nonspecific electrostatic sequestration by unstructured domains. Several investigators have postulated the existence of distinct pools of PIP2 within the cell to account for the myriad functions of this lipid. Recent experimental work indicates certain regions of the plasma membrane-membrane ruffles and nascent phagosomes-do indeed concentrate PIP2. We consider two mechanisms that could account for this phenomenon: local synthesis and electrostatic sequestration. We conclude by considering the hypothesis that proteins such as MARCKS bind a significant fraction of the PIP2 in a cell, helping to sequester it in lateral membrane domains, then release this lipid in response to local signals such as an increased concentration of Ca(++)/calmodulin or activation of protein kinase C.
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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 [4]
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“(20) discuss the (still imperfectly understood) roles that PIP 2,”
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- Authors
- McLaughlin, S., Wang, J., Gambhir, A., & Murray, D.
- Affiliations
- State University of New York (US)
- Venue
- Annual Review of Biophysics and Biomolecular Structure
- Publisher
- Annual Reviews
- Published
- 2002-06
- Volume
- 31
- Issue
- 1
- Pages
- 151-175
- ISSN
- 1056-8700 (ISSN-L)
- 1545-4266
- OpenAlex
- W2134283668
- Cited by
- 837
- References
- 2
- Citations by year
- 2026: 7 · 2025: 16 · 2024: 17 · 2023: 16 · 2022: 28 · 2021: 34 · 2020: 48 · 2019: 28 · 2018: 28 · 2017: 35 · 2016: 37 · 2015: 36 · 2014: 63 · 2013: 43 · 2012: 53
- FWCI
- 2.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Biophysics and Biomolecular Structure (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM 24971, T32GM008444)
- 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, protein-lipid interactions, ruffles, phagosome, MARCKS, lipid rafts, calcium/calmodulin signaling, protein kinase C, plasma membrane, lipid signaling
- MeSH terms
- Animals, Calmodulin, Cell Membrane, Cytoskeleton, Models, Molecular, Protein Kinase C, Signal Transduction, Protein Structure, Tertiary, Phosphatidylinositol 4,5-Diphosphate, Lipid Metabolism
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