Plasticity of PI4KIIIα interactions at the plasma membrane
Open accessAbstract
Plasma membrane PI4P is an important direct regulator of many processes that occur at the plasma membrane and also a biosynthetic precursor of PI(4,5)P2 and its downstream metabolites. The majority of this PI4P pool is synthesized by an evolutionarily conserved complex, which has as its core the PI 4-kinase PI4KIIIα (Stt4 in yeast) and also comprises TTC7 (Ypp1 in yeast) and the peripheral plasma membrane protein EFR3. While EFR3 has been implicated in the recruitment of PI4KIIIα via TTC7, the plasma membrane protein Sfk1 was also shown to participate in this targeting and activity in yeast. Here, we identify a member of the TMEM150 family as a functional homologue of Sfk1 in mammalian cells and demonstrate a role for this protein in the homeostatic regulation of PI(4,5)P2 at the plasma membrane. We also show that the presence of TMEM150A strongly reduces the association of TTC7 with the EFR3-PI4KIIIα complex, without impairing the localization of PI4KIIIα at the plasma membrane. Collectively our results suggest a plasticity of the molecular interactions that control PI4KIIIα localization and function.
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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 [19]
PI4KIIIα is present in a complex with TTC7 and EFR3 that allows targeting to the plasma membrane.
“PI4KIIIα is present in a complex with two adapter proteins, TTC7 (tetratricopeptide repeat domain 7) and EFR3 (protein encoded by the EFR3 gene) that allows targeting to the plasma membrane [19].”
From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [19]
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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
- Chung, J., Nakatsu, F., Baskin, J. M., & De Camilli, P.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- The EMBO Reports
- Published
- 2015-01-21
- Volume
- 16
- Issue
- 3
- Pages
- 312-320
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- PMC
- PMC4364870
- OpenAlex
- W2128726985
- Cited by
- 98
- References
- 1
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 4 · 2023: 7 · 2022: 13 · 2021: 11 · 2020: 20 · 2019: 4 · 2018: 11 · 2017: 3 · 2016: 8 · 2015: 3
- FWCI
- 4.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- EMBO Reports (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- NIH (R37NS036251, DK082700, DA018343, T32GM007223, K99GM110121)
- Simons Foundation
- Jane Coffin Childs Fund
- 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-phosphate, protein-protein interaction, phosphoinositide metabolism
- MeSH terms
- Cell Membrane, HeLa Cells, Homeostasis, Humans, Membrane Proteins, Peptide Termination Factors, Proteins, Immunoblotting, Minor Histocompatibility Antigens, Phosphotransferases (Alcohol Group Acceptor), Multiprotein Complexes, Immunoprecipitation
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