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A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
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Published on: March 15, 2016

VEGF activates NR2B phosphorylation through Dab1 pathway.

Kristy R Howell1, Md Nusrul Hoda, Anilkumar Pillai

  • 1Department of Psychiatry and Health Behavior, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA.

Neuroscience Letters
|August 7, 2013
PubMed
Summary
This summary is machine-generated.

Vascular endothelial growth factor (VEGF) signaling influences reelin pathways by regulating NMDA receptor activity. Disabled 1 (Dab1) acts as a key mediator in this cross-talk between VEGF and reelin signaling in neurons.

Keywords:
Dab1NR2BNeuronsReelinVEGF

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Signaling

Background:

  • Vascular endothelial growth factor (VEGF) and reelin are crucial signaling pathways in neuronal development.
  • Both VEGF and reelin independently regulate NMDA type glutamate receptor (NMDAR) activity.
  • The interaction between VEGF and reelin signaling in NMDAR regulation remains unclear.

Purpose of the Study:

  • To investigate the potential cross-talk between VEGF and reelin signaling pathways.
  • To elucidate the role of downstream signaling molecules in mediating this interaction.
  • To determine how VEGF influences reelin signaling and NMDAR activity.

Main Methods:

  • Utilized neuronal cell cultures and genetic models (reeler mice).
  • Investigated protein-protein interactions using co-immunoprecipitation.
  • Assessed receptor activation and downstream signaling events via Western blotting and biochemical assays.
  • Examined the effects of VEGF treatment on reelin-deficient neurons.

Main Results:

  • Disabled 1 (Dab1), a reelin pathway molecule, mediates VEGF-induced regulation of NMDAR subunit NR2B.
  • VEGF treatment induced association between VEGF receptor-2 (Flk1) and reelin receptor (ApoER2).
  • VEGF-induced activation of Dab1 and NR2B was dependent on Flk1.
  • VEGF treatment rescued deficits in phospho-Dab1 levels in reeler neurons.

Conclusions:

  • VEGF plays a significant role in regulating reelin signaling.
  • Dab1 is a critical molecular link in the cross-talk between VEGF and reelin signaling pathways.
  • This cross-talk is important for NMDAR regulation and neuronal function.