Encoding and Transducing the Synaptic or Extrasynaptic Origin of NMDA Receptor Signals to the Nucleus
| Autor: | Werner Zuschratter, Marina Mikhaylova, Eckart D. Gundelfinger, Jale Sahin, Philipp Bethge, Michael R. Kreutz, Thilo Kähne, Rahul Kaushik, Sujoy Bera, Christina Spilker, Thomas Behnisch, Vladan Rankovic, Michael Naumann, Anna Karpova, Julia Bär, Pasham Parameshwar Reddy |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
MAPK/ERK pathway
Programmed cell death Cell Survival MAP Kinase Signaling System Long-Term Potentiation Nerve Tissue Proteins Biology Hippocampus Receptors N-Methyl-D-Aspartate General Biochemistry Genetics and Molecular Biology Dephosphorylation 03 medical and health sciences Mice 0302 clinical medicine Intermediate Filament Proteins medicine Animals Phosphorylation Cyclic AMP Response Element-Binding Protein Cells Cultured 030304 developmental biology Cell Nucleus Neurons 0303 health sciences Biochemistry Genetics and Molecular Biology(all) Long-Term Synaptic Depression Neurodegeneration medicine.disease Phosphoric Monoester Hydrolases Cell biology Rats medicine.anatomical_structure Gene Expression Regulation Synaptic plasticity Synapses NMDA receptor Nucleus 030217 neurology & neurosurgery |
| Zdroj: | Cell. 152(5):1119-1133 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2013.02.002 |
| Popis: | SummaryThe activation of N-methyl-D-aspartate-receptors (NMDARs) in synapses provides plasticity and cell survival signals, whereas NMDARs residing in the neuronal membrane outside synapses trigger neurodegeneration. At present, it is unclear how these opposing signals are transduced to and discriminated by the nucleus. In this study, we demonstrate that Jacob is a protein messenger that encodes the origin of synaptic versus extrasynaptic NMDAR signals and delivers them to the nucleus. Exclusively synaptic, but not extrasynaptic, NMDAR activation induces phosphorylation of Jacob at serine-180 by ERK1/2. Long-distance trafficking of Jacob from synaptic, but not extrasynaptic, sites depends on ERK activity, and association with fragments of the intermediate filament α-internexin hinders dephosphorylation of the Jacob/ERK complex during nuclear transit. In the nucleus, the phosphorylation state of Jacob determines whether it induces cell death or promotes cell survival and enhances synaptic plasticity. |
| Databáze: | OpenAIRE |
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