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Phosphoinositides and membrane traffic in health and disease

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Regulatory Mechanisms of Intracellular Membrane Transport

Part of the book series: Topics in Current Genetics ((TCG,volume 10))

Abstract

The phosphorylated derivatives of phosphatidylinositol (PtdIns) are collectively known as the polyphosphoinositides (PIs) and they were originally identified as precursors of second messengers. In particular, PtdIns 4,5-bisphosphate (PtdIns45P2), initially the most studied of the PIs, was shown to be the substrate of a PI-specific phospholipase C (PI-PLC), which upon agonist stimulation generates the water-soluble inositol 1,4,5-trisphosphate and the membrane-bound diacylglycerol. Over the last decade or so, it has become increasingly clear that the PIs fulfil a wider variety of functions, including the control of cytoskeleton assembly and membrane traffic. This occurs via reversible phosphorylation of the inositol ring, which generates a series of products that can bind to cytosolic or membrane proteins with variable affinities and specificities. Indeed, the number of domains or modules that are known to specifically bind the various PIs, such as FYVE fingers, and PH, PX and ENTH domains, have increased dramatically over just the past few years. By interacting with these protein domains, membrane PIs can control actin cytoskeleton remodelling, vesicle coat assembly, and signalling-complex formation. Here, we give an overview of the functions of the PI-metabolizing enzymes in the secretory pathway, and of the human pathologies that are associated with mutations in these enzymes.

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  1. Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, Via Nazionale, 66030 Santa Maria Imbaro (Chieti), Italy

    Anna Godi, Antonella Di Campli & Maria Antonietta De Matteis

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  1. Anna Godi
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  2. Antonella Di Campli
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  3. Maria Antonietta De Matteis
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Correspondence to Anna Godi .

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Sirkka Keränen Jussi Jäntti

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Godi, A., Di Campli, A., De Matteis, M.A. Phosphoinositides and membrane traffic in health and disease. In: Keränen, S., Jäntti, J. (eds) Regulatory Mechanisms of Intracellular Membrane Transport. Topics in Current Genetics, vol 10. Springer, Berlin, Heidelberg. https://doi.org/10.1007/b98497

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  • DOI: https://doi.org/10.1007/b98497

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