Cited by 277Cellular transport and secretionLipid metabolism and biosynthesisProtein Kinase Regulation and GTPase Signaling
PtdIns4P synthesis by PI4KIIIα at the plasma membrane and its impact on plasma membrane identity
Open accessNakatsu, Fubito, Baskin, Jeremy M., Chung, Jeeyun, Tanner, Lukas B., Shui, Guanghou, Lee, Sang Yoon, Pirruccello, Michelle, Hao, Mingming +3 more·2012·Journal of Cell Biology
DOI 10.1083/jcb.201206095PMC PMC3518224
Abstract
Plasma membrane phosphatidylinositol (PI) 4-phosphate (PtdIns4P) has critical functions via both direct interactions and metabolic conversion to PI 4,5-bisphosphate (PtdIns(4,5)P2) and other downstream metabolites. However, mechanisms that control this PtdIns4P pool in cells of higher eukaryotes remain elusive. PI4KIIIα, the enzyme thought to synthesize this PtdIns4P pool, is reported to localize in the ER, contrary to the plasma membrane localization of its yeast homologue, Stt4. In this paper, we show that PI4KIIIα was targeted to the plasma membrane as part of an evolutionarily conserved complex containing Efr3/rolling blackout, which we found was a palmitoylated peripheral membrane protein. PI4KIIIα knockout cells exhibited a profound reduction of plasma membrane PtdIns4P but surprisingly only a modest reduction of PtdIns(4,5)P2 because of robust up-regulation of PtdIns4P 5-kinases. In these cells, however, much of the PtdIns(4,5)P2 was localized intracellularly, rather than at the plasma membrane as in control cells, along with proteins typically restricted to this membrane, revealing a major contribution of PI4KIIIα to the definition of plasma membrane identity.
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PI4KIIIα plays a major role in the generation of PI4P at the plasma membrane.
“Of the four enzymes, PI4K Type IIIα (PI4KIIIα) plays a major role in the generation of PI4P at the plasma membrane [19,20].”
From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [20]
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Ingolia, N. T., Lareau, L. F., & Weissman, J. S. (2011) · Cell · doi:10.1016/j.cell.2011.10.002 · Cited by 2,187 · see citing works
Self-citationMuscarinic acetylcholine receptors: mutant mice provide new insights for drug development
Wess, J., Eglen, R. M., & Gautam, D. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2379 · Cited by 637 · see citing works
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Structural Basis for Regulation of Phosphoinositide Kinases and Their Involvement in Human Disease
Burke, J. E. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.08.005 · Cited by 276 · see citing works
Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane
Katan, M., & Cockcroft, S. (2020) · Essays in Biochemistry · doi:10.1042/ebc20200041 · Cited by 176 · see citing works
- Authors
- Nakatsu, F., Baskin, J. M., Chung, J., Tanner, L. B., Shui, G., Lee, S. Y., Pirruccello, M., Hao, M., Ingolia, N. T., Wenk, M. R., & De Camilli, P.
- Affiliations
- Howard Hughes Medical Institute (US)
- National University of Singapore (SG)
- Department of Embryology (US)
- Department of Cell Biology 1 ; 2 ; 3 ; 4 ; and 5
- ORCID
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2012-12-10
- Volume
- 199
- Issue
- 6
- Pages
- 1003-1016
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC3518224
- OpenAlex
- W2119318973
- Cited by
- 277
- References
- 2
- Citations by year
- 2026: 10 · 2025: 19 · 2024: 14 · 2023: 22 · 2022: 24 · 2021: 27 · 2020: 33 · 2019: 21 · 2018: 19 · 2017: 14 · 2016: 23 · 2015: 19 · 2014: 19 · 2013: 13
- FWCI
- 7.73
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-sa)
- Funders
- American Diabetes Association
- Simons Foundation
- Yale University (T32GM007223)
- Searle Scholars Program
- National Research Foundation
- National Research Foundation Singapore
- National Institutes of Health (DA-018343, DK-45735)
- Biomedical Research Council
- National Institute on Drug Abuse (DA 018343, P30DA018343)
- National Institute of General Medical Sciences (T32GM007223)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-075772, DK 45735, DK078625, K01DK078625, DK082700, R01DK075772, P30DK045735, R01DK082700)
- National Institute of Neurological Disorders and Stroke (R37NS036251)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- PI4KIIIα, phosphatidylinositol 4,5-bisphosphate, membrane lipid metabolism, plasma membrane localization, phosphoinositide signaling
- MeSH terms
- Animals, Cell Membrane, Female, Fibroblasts, Genetic Vectors, HeLa Cells, Humans, Male, Mice, Inbred C57BL, Minor Histocompatibility Antigens, Up-Regulation, Phosphotransferases (Alcohol Group Acceptor), Phosphatidylinositol Phosphates, Electroporation, Mice, Knockout, Mice, Mice, 129 Strain
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