title: A model of neuregulin control of NMDA receptors on synaptic spines.
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.
authors.affiliation: The Brain and Mind Research Institute and The Centre for Mathematical Biology, The University of Sydney, Sydney, New South Wales, 2006, Australia. max.bennett@sydney.edu.au
authors.forename: Max R
authors.initials: MR
authors.lastname: Bennett
authors.forename: Les
authors.initials: L
authors.lastname: Farnell
authors.forename: William G
authors.initials: WG
authors.lastname: Gibson
mesh_terms: D000818:Animals; D049229:Dendritic Spines / Q000378:metabolism*; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000378:metabolism; D008959:Models, Neurological; D020890:Neuregulin-1 / Q000378:metabolism*; D010766:Phosphorylation; D066247:Receptor, ErbB-4; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D020890:Neuregulin-1; D016194:Receptors, N-Methyl-D-Aspartate; D066246:ErbB Receptors; D066247:Receptor, ErbB-4; D019061:src-Family Kinases