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The multifaceted role of PIP2 in leukocyte biology

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Abstract

Phosphatidylinositol 4,5-bisphosphate (PIP2) represents about 1 % of plasma membrane phospholipids and behaves as a pleiotropic regulator of a striking number of fundamental cellular processes. In recent years, an increasing body of literature has highlighted an essential role of PIP2 in multiple aspects of leukocyte biology. In this emerging picture, PIP2 is envisaged as a signalling intermediate itself and as a membrane-bound regulator and a scaffold of proteins with specific PIP2 binding domains. Indeed PIP2 plays a key role in several functions. These include directional migration in neutrophils, integrin-dependent adhesion in T lymphocytes, phagocytosis in macrophages, lysosomes secretion and trafficking at immune synapse in cytolytic effectors and secretory cells, calcium signals and gene transcription in B lymphocytes, natural killer cells and mast cells. The coordination of these different aspects relies on the spatio-temporal organisation of distinct PIP2 pools, generated by the main PIP2 generating enzyme, phosphatidylinositol 4-phosphate 5-kinase (PIP5K). Three different isoforms of PIP5K, named α, β and γ, and different splice variants have been described in leukocyte populations. The isoform-specific coupling of specific isoforms of PIP5K to different families of activating receptors, including integrins, Fc receptors, toll-like receptors and chemokine receptors, is starting to be reported. Furthermore, PIP2 is turned over by multiple metabolising enzymes including phospholipase C (PLC) γ and phosphatidylinositol 3-kinase (PI3K) which, along with Rho family small G proteins, is widely involved in strategic functions within the immune system. The interplay between PIP2, lipid-modifying enzymes and small G protein-regulated signals is also discussed.

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Acknowledgments

This work was supported by grants from Italian Association for Cancer Research (AIRC and AIRC 5 × 1000), the Italian Ministry for University and Research (MIUR), the Center of Excellence (BEMM) and the Fondazione Italiana Sclerosi Multipla (Project No. FISM 2011/R/36).

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Authors and Affiliations

  1. Department of Biology and Biotechnology “Charles Darwin”, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, Via dei Sardi 70, 00185, Rome, Italy

    Loretta Tuosto & Michela Muscolini

  2. Department of Experimental Medicine, Sapienza University, Viale Regina Elena 324, 00185, Rome, Italy

    Cristina Capuano & Ricciarda Galandrini

  3. Department of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, Viale Regina Elena 291, 00185, Rome, Italy

    Angela Santoni

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  1. Loretta Tuosto
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  2. Cristina Capuano
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  5. Ricciarda Galandrini
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Correspondence to Loretta Tuosto or Ricciarda Galandrini.

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Tuosto, L., Capuano, C., Muscolini, M. et al. The multifaceted role of PIP2 in leukocyte biology. Cell. Mol. Life Sci. 72, 4461–4474 (2015). https://doi.org/10.1007/s00018-015-2013-0

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