A Plethora of Functions Condensed into Tiny Phospholipids: The Story of PI4P and PI(4,5)P2
Abstract
1. Introduction
The (re)Birth of PI4P and PI(4,5)P2
2. PI4Ks
2.1. PI4KIIα
2.2. PI4KIIβ
2.3. PI4Kα
2.4. PI4Kβ
3. PI4P5KIs
3.1. PI4P5KIα
3.2. PI4P5KIβ
3.3. PI4P5KIγ
4. PI4P: A Huge Burden on a Small Lipid
4.1. PI4P at the Golgi Apparatus: Glycosylation and Anterograde Trafficking
4.2. PI4P at the Plasma Membrane
4.3. PI4P at Membrane-Contact Sites
5. PI(4,5)P2: A Dual Role
5.1. PI(4,5)P2 in Clathrin-Mediated Endocytosis
5.2. PI(4,5)P2 as a Signaling Molecule
6. Tools for Detection of Intracellular Phosphoinositides
6.1. Antibodies
6.2. Genetically Encoded Probes
6.3. Mass Spectrometry
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Target Enzyme | Inhibitor | Target IC50 (nM) | Off-Targets, IC50 (nM) | State of Clinical Development | Research Area | References |
---|---|---|---|---|---|---|
PI4KIIα | PI-273 | 470 [48] | no off-targets, highly selective | in vitro | cancer | [48,67] |
in vivo | [48] | |||||
PI4KIIIα | GSK-A1 | 3.1 [15] | >310 [15] | in vitro | basic | [68,69] |
cancer | [70] | |||||
viral infection | [71] | |||||
inflammation | [72] | |||||
neuronal plasticity | [73] | |||||
myelination | [74] | |||||
GSK-F1 | 16 [15] | PI4KIIIβ, PI3Ks >1600 [15] | in vitro | cancer | [75] | |
in vivo | basic | [68] | ||||
PI4KIIIβ | IN-9 | 7 [76] | PI4KIIIα, PI3Ks >150 [76] | in vitro | cancer | [67] |
inflammation | [72] | |||||
IN-10 | 3.6 [15] | PI4KIIIα, PI3Ks >720 [15,33] | in vitro | inflammation | [72] | |
T-00127-HEV1 | 60 [32] | PI4KIIIα, PIK3CD 10 000 [32] | in vitro | viral infection | [77,78,79] | |
in vivo | [78] | |||||
BF738735 | 5.7 [32] | PI4KIIIα 1700 [33] | in vitro | viral infection | [79,80] | |
Enviroxime | 120 [32] | PI4KIIIα 1400 [32] | discontinued in phase II clinical trials | viral infection | [15,81] | |
Plasmodium falciparum PI4KIIIβ | MMV390048 | 28 [82] | no off-targets, highly selective | terminated phase II clinical trials | parasitic infection | [15,83] |
PI4P5KIα | ISA-2011B | n.d. [15] | p110α n.d. [15] | in vitro | inflammation | [84] |
cancer | [85,86] | |||||
in vivo | cancer | [85,86] | ||||
PI4P5KIγ | UNC3230 | 51 (Kd) [15] | PI5P4Kγ 4 (Kd) [15] | in vitro | cancer | [87] |
PI | Protein Domain | Intracellular Localization |
---|---|---|
PI4P | OSH2-PH [144] | PM |
OSBP-PH [145] | Golgi | |
FAPP1-PH [121] | Golgi | |
P4M SidM [118] | Golgi, PM, LE/Lys | |
PI(4,5)P2 | PLCδ1-PH [146] | PM |
Tubby-PX [147] | PM | |
Epsin1-ENTH/AP180-ANTH [148,149] | PM |
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Bura, A.; Čabrijan, S.; Đurić, I.; Bruketa, T.; Jurak Begonja, A. A Plethora of Functions Condensed into Tiny Phospholipids: The Story of PI4P and PI(4,5)P2. Cells 2023, 12, 1411. https://doi.org/10.3390/cells12101411
Bura A, Čabrijan S, Đurić I, Bruketa T, Jurak Begonja A. A Plethora of Functions Condensed into Tiny Phospholipids: The Story of PI4P and PI(4,5)P2. Cells. 2023; 12(10):1411. https://doi.org/10.3390/cells12101411
Chicago/Turabian StyleBura, Ana, Sara Čabrijan, Iris Đurić, Tea Bruketa, and Antonija Jurak Begonja. 2023. "A Plethora of Functions Condensed into Tiny Phospholipids: The Story of PI4P and PI(4,5)P2" Cells 12, no. 10: 1411. https://doi.org/10.3390/cells12101411
APA StyleBura, A., Čabrijan, S., Đurić, I., Bruketa, T., & Jurak Begonja, A. (2023). A Plethora of Functions Condensed into Tiny Phospholipids: The Story of PI4P and PI(4,5)P2. Cells, 12(10), 1411. https://doi.org/10.3390/cells12101411