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The Role of Phosphoinositides in Synapse Function

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Abstract

Since the discovery of phosphatidylinositol-3-kinase, scientific interest in the biological functions of phosphoinositides has greatly increased. Currently, seven phosphoinositides have been identified. These phosphoinositides are specifically localized to organelle membranes, their site of action. Phosphoinositides can regulate neuronal function by specifically recruiting downstream proteins that have phosphoinositide-binding domains. To date, it is well accepted that phosphoinositides play important roles in a broad spectrum of neuronal functions from regulating neural development to modulating synapse function. This review will provide an overview of the function and distribution of phosphoinositides at synapses.

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Abbreviations

PIP3:

Phosphatidylinositol 3,4,5-trisphosphate

PI(4,5)P2:

Phosphatidylinositol 4,5-bisphosphate

PI(3,4)P2:

Phosphatidylinositol 3,4-bisphosphate

PI(3,5)P2:

Phosphatidylinositol 3,5-bisphosphate

PI(4)P:

Phosphatidylinositol 4-phosphate

PI(3)P:

Phosphatidylinositol 3-phosphate

PI(5)P:

Phosphatidylinositol 5-phosphate

PI3K:

Phosphatidylinositol 3-kinase

PI4K:

Phosphatidylinositol 4-kinase

PI(4)P5K:

Phosphatidylinositol 4-phosphate 5-kinase

PI(5)P4K:

Phosphatidylinositol 5-phosphate 4-kinase

PI:

Phosphatidylinositol

FRET:

Förster resonance energy transfer

AMPAR:

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor

NMDAR:

N-methyl-d-aspartate receptor

CaMKII:

Ca2+/calmodulin-dependent protein kinase II

LTP:

Long-term potentiation

LTD:

Long-term depression

SHIP:

Src homology 2-containing inositol 5′-phosphatase

IP3:

Inositol 1,4,5-trisphosphate

ER:

Endoplasmic reticulum

FAPP2:

PI(4)P adaptor protein 2

PTEN:

Phosphatase and tensin homolog

Fig4:

Factor-induced gene

MTMR:

Myotubularin-related protein 2

OCRL:

Oculocerebrorenal syndrome of Lowe

INPP4A:

Inositol polyphosphate 4-phosphatase 4a

PLIP:

PTEN-like phosphatase

OSBP:

Oxysterol-binding protein

CERT:

Ceremide transfer protein

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Acknowledgements

I am grateful to L. Yu and F. Hullin-Matsuda for comments on the manuscript. I also thank the members of Hayashi’s laboratory for their support, critical reading of the manuscript and discussion. This work was supported by a Grant-in-Aid for Young Scientists (B) and the RIKEN Special Postdoctoral Researcher Program.

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Correspondence to Yoshibumi Ueda.

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Ueda, Y. The Role of Phosphoinositides in Synapse Function. Mol Neurobiol 50, 821–838 (2014). https://doi.org/10.1007/s12035-014-8768-8

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  • DOI: https://doi.org/10.1007/s12035-014-8768-8

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