The multifaceted role of PIP2 in leukocyte biology
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  • 作者:Loretta Tuosto ; Cristina Capuano ; Michela Muscolini…
  • 关键词:Phosphoinositide ; Phosphatidylinositol 4 ; phosphate 5 ; kinase ; Immune cell functions ; Molecular signals ; Cytoskeleton reorganisation
  • 刊名:Cellular and Molecular Life Sciences (CMLS)
  • 出版年:2015
  • 出版时间:December 2015
  • 年:2015
  • 卷:72
  • 期:23
  • 页码:4461-4474
  • 全文大小:1,653 KB
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  • 作者单位:Loretta Tuosto (1)
    Cristina Capuano (2)
    Michela Muscolini (1)
    Angela Santoni (3)
    Ricciarda Galandrini (2)

    1. Department of Biology and Biotechnology “Charles Darwin”, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, Via dei Sardi 70, 00185, Rome, Italy
    2. Department of Experimental Medicine, Sapienza University, Viale Regina Elena 324, 00185, Rome, Italy
    3. Department of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, Viale Regina Elena 291, 00185, Rome, Italy
  • 刊物类别:Biomedical and Life Sciences
  • 刊物主题:Life Sciences
    Cell Biology
    Biomedicine
    Life Sciences
    Biochemistry
  • 出版者:Birkh盲user Basel
  • ISSN:1420-9071
文摘
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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