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Bulletin of Mathematical Biology

, Volume 74, Issue 3, pp 717–735 | Cite as

A Model of Neuregulin Control of NMDA Receptors on Synaptic Spines

  • Max R. BennettEmail author
  • Les Farnell
  • William G. Gibson
Original Article

Abstract

Neuregulin (Nrg) through its receptor ErbB4 modulates the activity of the N-Methyl-D-Aspartate (NMDA) receptor (NMDAR) at synapses. As modification of this pathway has been implicated in schizophrenia, it is of great interest to define it in precise quantitative terms. Kinetic models of the epidermal growth factor (EGF)/ErbB receptor signalling pathway describing activation, desensitization, and tyrosine phosphorylation of EGFR/ErbB followed by binding and activation of Src family kinases that is subsequently followed by phosphorylation of target proteins are available. We have adapted these to give a kinetic description of NMDAR modulation by Nrg that recapitulates the observed kinetics of autophosphorylation of the ErbB dimer as well as the modulation of the NMDAR by Src kinase, according to whether the kinases are activated or deactivated. This quantitative description of the Nrg/NMDAR pathway provides a model for experimental elucidation of what goes awry in animal models of schizophrenia.

Keywords

ErbB Phosphorylation Src kinase 

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Copyright information

© Society for Mathematical Biology 2011

Authors and Affiliations

  • Max R. Bennett
    • 1
    Email author
  • Les Farnell
    • 2
  • William G. Gibson
    • 2
  1. 1.The Brain and Mind Research Institute and The Centre for Mathematical BiologyThe University of SydneySydneyAustralia
  2. 2.The School of Mathematics and Statistics and The Centre for Mathematical BiologyThe University of SydneySydneyAustralia

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