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.

The multifaceted role of PIP2 in leukocyte biology / Tuosto, Loretta; Capuano, Cristina; Muscolini, Michela; Santoni, Angela; Galandrini, Ricciarda. - In: CELLULAR AND MOLECULAR LIFE SCIENCES. - ISSN 1420-682X. - ELETTRONICO. - 72:23(2015), pp. 4461-4474. [10.1007/s00018-015-2013-0]

The multifaceted role of PIP2 in leukocyte biology

TUOSTO, Loretta
Primo
Writing – Original Draft Preparation
;
CAPUANO, CRISTINA
Secondo
Writing – Review & Editing
;
MUSCOLINI, MICHELA
Writing – Review & Editing
;
SANTONI, Angela
Penultimo
Writing – Review & Editing
;
GALANDRINI, Ricciarda
Ultimo
Writing – Review & Editing
2015

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.
2015
Cytoskeleton reorganisation; Immune cell functions; Molecular signals; Phosphatidylinositol 4-phosphate 5-kinase; Phosphoinositide
01 Pubblicazione su rivista::01a Articolo in rivista
The multifaceted role of PIP2 in leukocyte biology / Tuosto, Loretta; Capuano, Cristina; Muscolini, Michela; Santoni, Angela; Galandrini, Ricciarda. - In: CELLULAR AND MOLECULAR LIFE SCIENCES. - ISSN 1420-682X. - ELETTRONICO. - 72:23(2015), pp. 4461-4474. [10.1007/s00018-015-2013-0]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/789872
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