Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at https://www.ucl.ac.uk/finance/research/rs-contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
Modulation of inositol polyphosphate levels regulates neuronal differentiation.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Loss O, Wu CT, Riccio A, Saiardi A
  • Publication date:
  • Pagination:
    2981, 2989
  • Journal:
    Mol Biol Cell
  • Volume:
  • Issue:
  • Status:
  • Country:
    United States
  • PII:
  • Language:
  • Keywords:
    Animals, Apoptosis, Caspase 3, Cell Differentiation, Cell Survival, Enzyme Activation, Gene Expression Regulation, Gene Knockdown Techniques, Inositol 1,4,5-Trisphosphate, Inositol Phosphates, Nerve Growth Factors, Neurons, PC12 Cells, Phosphotransferases (Alcohol Group Acceptor), Phytic Acid, Rats, Sympathetic Nervous System
The binding of neurotrophins to tropomyosin receptor kinase receptors initiates several signaling pathways, including the activation of phospholipase C-γ, which promotes the release of diacylglycerol and inositol 1,4,5-trisphosphate (IP(3)). In addition to recycling back to inositol, IP(3) serves as a precursor for the synthesis of higher phosphorylated inositols, such as inositol 1,3,4,5,6-pentakisphosphate (IP(5)) and inositol hexakisphosphate (IP(6)). Previous studies on the effect of neurotrophins on inositol signaling were limited to the analysis of IP(3) and its dephosphorylation products. Here we demonstrate that nerve growth factor (NGF) regulates the levels of IP(5) and IP(6) during PC12 differentiation. Furthermore, both NGF and brain-derived neurotrophic factor alter IP(5) and IP(6) intracellular ratio in differentiated PC12 cells and primary neurons. Neurotrophins specifically regulate the expression of IP(5)-2 kinase (IP(5)-2K), which phosphorylates IP(5) into IP(6). IP(5)-2K is rapidly induced after NGF treatment, but its transcriptional levels sharply decrease in fully differentiated PC12 cells. Reduction of IP(5)-2K protein levels by small interfering RNA has an effect on the early stages of PC12 cell differentiation, whereas fully differentiated cells are not affected. Conversely, perturbation of IP(5)-2K levels by overexpression suggests that both differentiated PC12 cells and sympathetic neurons require low levels of the enzyme for survival. Therefore maintaining appropriate intracellular levels of inositol polyphosphates is necessary for neuronal survival and differentiation.
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers
MRC/UCL Lab for Molecular Cell Bio
MRC/UCL Lab for Molecular Cell Bio
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by