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Phosphoinositides in cell regulation and membrane dynamics

Abstract

Inositol phospholipids have long been known to have an important regulatory role in cell physiology. The repertoire of cellular processes known to be directly or indirectly controlled by this class of lipids has now dramatically expanded. Through interactions mediated by their headgroups, which can be reversibly phosphorylated to generate seven species, phosphoinositides play a fundamental part in controlling membrane–cytosol interfaces. These lipids mediate acute responses, but also act as constitutive signals that help define organelle identity. Their functions, besides classical signal transduction at the cell surface, include regulation of membrane traffic, the cytoskeleton, nuclear events and the permeability and transport functions of membranes.

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Figure 1: Metabolism and subcellular distribution of phosphoinositides.
Figure 2: Coincidence detection in phosphoinositide signalling.
Figure 3: Cartoons illustrating examples of functional interplay between phosphoinositides and small GTPases.
Figure 4: Examples of processes regulated by PtdIns(4,5)P 2 at the plasma membrane.

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Acknowledgements

We thank N. Borgese, V. Haucke and O. Cremona for critical reading of the manuscript. We also thank B. Chang for providing the fluorescence images in Fig. 1 and for her comments on the manuscript. DNA constructs were gifts from H. Stenmark, T. Meyer and A. De Matteis. We apologize to all the scientists whose original studies and reviews were not quoted in our manuscript owing to space limitations. G.D.P. is funded by grants from the National Institute of Health. P.D.C is funded by the HHMI and by grants from the National Institute of Health, the Yale Center for Genomics and Proteomics, the Yale/NIDA Neuroproteomics Center and the G. Harold and Leila Y. Mathers Charitable Foundation.

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Di Paolo, G., De Camilli, P. Phosphoinositides in cell regulation and membrane dynamics. Nature 443, 651–657 (2006). https://doi.org/10.1038/nature05185

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