caa a22 4500 606177035 CHVBK 20210128100750.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s00018-015-2013-0 doi (NATIONALLICENCE)springer-10.1007/s00018-015-2013-0 The multifaceted role of PIP2 in leukocyte biology [Elektronische Daten] [Loretta Tuosto, Cristina Capuano, Michela Muscolini, Angela Santoni, Ricciarda Galandrini] 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. Springer Basel, 2015 Phosphoinositide nationallicence Phosphatidylinositol 4-phosphate 5-kinase nationallicence Immune cell functions nationallicence Molecular signals nationallicence Cytoskeleton reorganisation nationallicence Tuosto Loretta Department of Biology and Biotechnology "Charles Darwin”, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, Via dei Sardi 70, 00185, Rome, Italy aut Capuano Cristina Department of Experimental Medicine, Sapienza University, Viale Regina Elena 324, 00185, Rome, Italy aut Muscolini Michela Department of Biology and Biotechnology "Charles Darwin”, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, Via dei Sardi 70, 00185, Rome, Italy aut Santoni Angela Department of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, Viale Regina Elena 291, 00185, Rome, Italy aut Galandrini Ricciarda Department of Experimental Medicine, Sapienza University, Viale Regina Elena 324, 00185, Rome, Italy aut Cellular and Molecular Life Sciences Springer International Publishing 72/23(2015-12-01), 4461-4474 1420-682X 72:23<4461 2015 72 18 https://doi.org/10.1007/s00018-015-2013-0 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 review-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-015-2013-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Tuosto Loretta Department of Biology and Biotechnology "Charles Darwin”, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, Via dei Sardi 70, 00185, Rome, Italy aut NATIONALLICENCE 700 1- Capuano Cristina Department of Experimental Medicine, Sapienza University, Viale Regina Elena 324, 00185, Rome, Italy aut NATIONALLICENCE 700 1- Muscolini Michela Department of Biology and Biotechnology "Charles Darwin”, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, Via dei Sardi 70, 00185, Rome, Italy aut NATIONALLICENCE 700 1- Santoni Angela Department of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, Viale Regina Elena 291, 00185, Rome, Italy aut NATIONALLICENCE 700 1- Galandrini Ricciarda Department of Experimental Medicine, Sapienza University, Viale Regina Elena 324, 00185, Rome, Italy aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer International Publishing 72/23(2015-12-01), 4461-4474 1420-682X 72:23<4461 2015 72 18