TY  - JOUR
Y1  - 2013/09/15/
ID  - discovery10162531
SN  - 1059-1524
A1  - Loss, Omar
A1  - Wu, Chun Ting
A1  - Riccio, Antonella
A1  - Saiardi, Adolfo
PB  - AMER SOC CELL BIOLOGY
N1  - © 2013 Loss et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available
to the public under an Attribution?Noncommercial?Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
IS  - 18
JF  - Molecular Biology of the Cell
UR  - https://doi.org/10.1091/mbc.E13-04-0198
EP  - 2989
TI  - Modulation of inositol polyphosphate levels regulates neuronal differentiation
SP  - 2981
AV  - public
KW  - Science & Technology
KW  -  Life Sciences & Biomedicine
KW  -  Cell Biology
KW  -  NERVE GROWTH-FACTOR
KW  -  1
KW  - 3
KW  - 4
KW  - 5
KW  - 6-PENTAKISPHOSPHATE 2-KINASE
KW  -  NEUROTROPHIC FACTOR
KW  -  SIGNALING PATHWAYS
KW  -  RETROGRADE SIGNAL
KW  -  DENDRITIC GROWTH
KW  -  FACTOR RECEPTOR
KW  -  MESSENGER-RNA
KW  -  PC12 CELLS
KW  -  HEXAKISPHOSPHATE
VL  - 24
N2  - The binding of neurotrophins to tropomyosin receptor kinase receptors initiates several signaling pathways, including the activation of phospholipase C-?, which promotes the release of diacylglycerol and inositol 1,4,5-trisphosphate (IP3). In addition to recycling back to inositol, IP3 serves as a precursor for the synthesis of higher phosphorylated inositols, such as inositol 1,3,4,5,6-pentakisphosphate (IP5) and inositol hexakisphosphate (IP6). 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 IP5 and IP6 during PC12 differentiation. Furthermore, both NGF and brain-derived neurotrophic factor alter IP5 and IP6 intracellular ratio in differentiated PC12 cells and primary neurons. Neurotrophins specifically regulate the expression of IP5-2 kinase (IP5-2K), which phosphorylates IP5 into IP6. IP5-2K is rapidly induced after NGF treatment, but its transcriptional levels sharply decrease in fully differentiated PC12 cells. Reduction of IP5-2K 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 IP5-2K 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. © 2013 Loss et al.
ER  -