The multifaceted role of PIP2 in leukocyte biology.
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.
Department of Biology and Biotechnology "Charles Darwin", Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, Via dei Sardi 70, 00185, Rome, Italy. loretta.tuosto@uniroma1.it.
Loretta
L
Tuosto
Department of Experimental Medicine, Sapienza University, Viale Regina Elena 324, 00185, Rome, Italy.
Cristina
C
Capuano
Department of Biology and Biotechnology "Charles Darwin", Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, Via dei Sardi 70, 00185, Rome, Italy.
Michela
M
Muscolini
Department of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, Viale Regina Elena 291, 00185, Rome, Italy.
Angela
A
Santoni
Department of Experimental Medicine, Sapienza University, Viale Regina Elena 324, 00185, Rome, Italy. ricciarda.galandrini@uniroma1.it.
Ricciarda
R
Galandrini
D000818:Animals; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology* / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000502:physiology*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction
D019269:Phosphatidylinositol 4,5-Diphosphate; D011494:Protein Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase
Cytoskeleton reorganisation; Immune cell functions; Molecular signals; Phosphatidylinositol 4-phosphate 5-kinase; Phosphoinositide