title: Bi-directional regulation of postsynaptic cortactin distribution by BDNF and NMDA receptor activity.
abstract: Abstract Cortactin is an F-actin-associated protein which interacts with the postsynaptic scaffolding protein Shank at the SH3 domain and is localized within the dendritic spine in the mouse neuron. Green fluorescent protein (GFP)-based time-lapse imaging revealed cortactin redistribution from dendritic cytoplasm to postsynaptic sites by application of brain-derived neurotrophic factor (BDNF). This response was mediated by mitogen-activated protein (MAP) kinase activation and was dependent on the C-terminal SH3 domain. In contrast, activation of N-methyl-D-aspartate (NMDA) receptors induced loss of cortactin from postsynaptic sites. This NMDA-dependent redistribution was blocked by an Src family kinase inhibitor. Conversely, increasing Src family kinase activity induced cortactin phosphorylation and loss of cortactin from the postsynaptic sites. Finally, blocking of endogenous BDNF reduced the amount of cortactin at the postsynaptic sites and an NMDA receptor antagonist prevented this reduction. These results indicate the importance of counterbalance between BDNF and NMDA receptor-mediated signalling in the reorganization of the postsynaptic actin cytoskeleton during neuronal development.
authors.affiliation: Department of Cell Biology, School of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, 113-8519, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Iki
authors.forename: Akihiro
authors.initials: A
authors.lastname: Inoue
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Bito
authors.forename: Shigeo
authors.initials: S
authors.lastname: Okabe
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015153:Blotting, Western / Q000379:methods; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D051356:Cortactin / Q000235:genetics / Q000378:metabolism*; D047630:Depsipeptides / Q000494:pharmacology; D000076122:Disks Large Homolog 4 Protein; D004347:Drug Interactions; D054637:Dual-Specificity Phosphatases; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051528:Guanylate Kinases; D006624:Hippocampus / Q000166:cytology; D000072233:Homer Scaffolding Proteins; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D016296:Mutagenesis / Q000502:physiology; D009154:Mutation / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D020813:Receptor, trkB / Q000276:immunology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection / Q000379:methods; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism; D018909:src Homology Domains / Q000502:physiology
chemical_list: C412373:AG 1879; D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor; D002352:Carrier Proteins; D051356:Cortactin; D047630:Depsipeptides; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D000072233:Homer Scaffolding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011743:Pyrimidines; D016194:Receptors, N-Methyl-D-Aspartate; C493465:Slc17a7 protein, mouse; D050598:Vesicular Glutamate Transport Protein 1; C057531:jasplakinolide; D049452:Green Fluorescent Proteins; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D006861:Hydrogen Peroxide; D020813:Receptor, trkB; D051528:Guanylate Kinases; D010749:Phosphoprotein Phosphatases; C489855:dual specificity phosphatase 12; D054637:Dual-Specificity Phosphatases