Regulation of distinct AMPA receptor phosphorylation sites during bidirectional synaptic plasticity
| Autor: | Michaela Barbarosie, Kimihiko Kameyama, Hey Kyoung Lee, Mark F. Bear, Richard L. Huganir |
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| Rok vydání: | 2000 |
| Předmět: |
Male
medicine.medical_specialty Long-Term Potentiation Models Neurological AMPA receptor In Vitro Techniques Biology Hippocampus Synapse Mice Internal medicine Ca2+/calmodulin-dependent protein kinase Serine LTP induction medicine Animals Rats Long-Evans Receptors AMPA Enzyme Inhibitors Phosphorylation Long-term depression Protein Kinase C Binding Sites Neuronal Plasticity Multidisciplinary musculoskeletal neural and ocular physiology Long-term potentiation Rats Cell biology Electrophysiology Endocrinology nervous system Calcium-Calmodulin-Dependent Protein Kinases Synapses Synaptic plasticity Calcium-Calmodulin-Dependent Protein Kinase Type 2 Synaptic tagging Signal Transduction |
| Zdroj: | Nature. 405:955-959 |
| ISSN: | 1476-4687 0028-0836 |
| Popis: | Bidirectional changes in the efficacy of neuronal synaptic transmission, such as hippocampal long-term potentiation (LTP) and long-term depression (LTD), are thought to be mechanisms for information storage in the brain. LTP and LTD may be mediated by the modulation of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazloe proprionic acid) receptor phosphorylation. Here we show that LTP and LTD reversibly modify the phosphorylation of the AMPA receptor GluR1 subunit. However, contrary to the hypothesis that LTP and LTD are the functional inverse of each other, we find that they are associated with phosphorylation and dephosphorylation, respectively, of distinct GluR1 phosphorylation sites. Moreover, the site modulated depends on the stimulation history of the synapse. LTD induction in naive synapses dephosphorylates the major cyclic-AMP-dependent protein kinase (PKA) site, whereas in potentiated synapses the major calcium/calmodulin-dependent protein kinase II (CaMKII) site is dephosphorylated. Conversely, LTP induction in naive synapses and depressed synapses increases phosphorylation of the CaMKII site and the PKA site, respectively. LTP is differentially sensitive to CaMKII and PKA inhibitors depending on the history of the synapse. These results indicate that AMPA receptor phosphorylation is critical for synaptic plasticity, and that identical stimulation conditions recruit different signal-transduction pathways depending on synaptic history. |
| Databáze: | OpenAIRE |
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