Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation
Open accessAbstract
Phosphoinositides (PIs) make up only a small fraction of cellular phospholipids, yet they control almost all aspects of a cell's life and death. These lipids gained tremendous research interest as plasma membrane signaling molecules when discovered in the 1970s and 1980s. Research in the last 15 years has added a wide range of biological processes regulated by PIs, turning these lipids into one of the most universal signaling entities in eukaryotic cells. PIs control organelle biology by regulating vesicular trafficking, but they also modulate lipid distribution and metabolism via their close relationship with lipid transfer proteins. PIs regulate ion channels, pumps, and transporters and control both endocytic and exocytic processes. The nuclear phosphoinositides have grown from being an epiphenomenon to a research area of its own. As expected from such pleiotropic regulators, derangements of phosphoinositide metabolism are responsible for a number of human diseases ranging from rare genetic disorders to the most common ones such as cancer, obesity, and diabetes. Moreover, it is increasingly evident that a number of infectious agents hijack the PI regulatory systems of host cells for their intracellular movements, replication, and assembly. As a result, PI converting enzymes began to be noticed by pharmaceutical companies as potential therapeutic targets. This review is an attempt to give an overview of this enormous research field focusing on major developments in diverse areas of basic science linked to cellular physiology and disease.
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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 [8]
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 [8]
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 [8]
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 [8]
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 [8]
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- Authors
- Balla, T.
- Affiliations
- Section on Molecular Signal Transduction, Program for Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
- Venue
- Physiological Reviews
- Publisher
- American Physiological Society
- Published
- 2013-07
- Volume
- 93
- Issue
- 3
- Pages
- 1019-1137
- ISSN
- 0031-9333 (ISSN-L)
- 1522-1210
- PMC
- PMC3962547
- OpenAlex
- W2162228329
- Cited by
- 1,638
- References
- 38
- Citations by year
- 2026: 115 · 2025: 122 · 2024: 117 · 2023: 149 · 2022: 144 · 2021: 150 · 2020: 152 · 2019: 142 · 2018: 126 · 2017: 105 · 2016: 127 · 2015: 112 · 2014: 67 · 2013: 8
- FWCI
- 12.08
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Physiological Reviews (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- phosphoinositides, lipid signaling, plasma membrane signaling, vesicle trafficking, lipid transfer proteins, ion channels, endocytosis, exocytosis, phosphoinositide metabolism, infectious agents, cancer, obesity, diabetes mellitus, genetic disorders
- MeSH terms
- Animals, Cell Communication, Gene Expression Regulation, Phosphatidylinositols, Molecular Structure
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