4.5 Review

Novel roles of phosphoinositides in signaling, lipid transport, and disease

Journal

CURRENT OPINION IN CELL BIOLOGY
Volume 63, Issue -, Pages 57-67

Publisher

CURRENT BIOLOGY LTD
DOI: 10.1016/j.ceb.2019.12.007

Keywords

Phosphoinositides; PIK3CA; PI4KB; GPCR; Flippases; Ion channels; Lipid signaling; PI3P; PI4P; PIP2; PIP3; Phosphatidylinositol; Membrane trafficking; Lipid transfer proteins; Membrane contact sites; Lipid kinases; Phosphoinositide kinases

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Funding

  1. Canadian Institute of Helath Research [CRN-142393]
  2. Natural Science and Engineering Research Council of Canada [2014-05218]
  3. Cancer Research Society [CRS 24368]
  4. CIHR
  5. Michael Smith Foundation for Health Research [17686]
  6. National Institutes of Health [1R35GM119412-01]

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Phosphoinositides (PPIns) are lipid signaling molecules that act as master regulators of cellular signaling. Recent studies have revealed novel roles of PPIns in myriad cellular processes and multiple human diseases mediated by misregulation of PPIn signaling. This review will present a timely summary of recent discoveries in PPIn biology, specifically their role in regulating unexpected signaling pathways, modification of signaling outcomes downstream of integral membrane proteins, and novel roles in lipid transport. This has revealed new roles of PPIns in regulating membrane trafficking, immunity, cell polarity, and response to extracellular signals. A specific focus-will be on novel opportunities to target PPIn metabolism for treatment of human diseases, including cancer, pathogen infection, developmental disorders, and immune disorders.

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