SynGAP-MUPP1-CaMKII Synaptic Complexes Regulate p38 MAP Kinase Activity and NMDA Receptor- Dependent Synaptic AMPA Receptor Potentiation
| Autor: | Luba Krapivinsky, David E. Clapham, Grigory Krapivinsky, Igor Medina, Svetlana Gapon |
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| Přispěvatelé: | Howard Hughes Medical Institute Children's Hospital, Epilepsie et ischémie cérébrale, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Tyzio, Roman |
| Rok vydání: | 2004 |
| Předmět: |
MESH: Hippocampus
MESH: Amino Acid Sequence MESH: GTPase-Activating Proteins SYNGAP1 Hippocampus Synaptic Transmission p38 Mitogen-Activated Protein Kinases MESH: Synapses Synapse MESH: Animals MESH: Nerve Tissue Proteins musculoskeletal neural and ocular physiology General Neuroscience GTPase-Activating Proteins Intracellular Signaling Peptides and Proteins Long-term potentiation Cell biology ras GTPase-Activating Proteins MESH: Calcium-Calmodulin-Dependent Protein Kinase Type 2 NMDA receptor Mitogen-Activated Protein Kinases MESH: Rats Neuroscience(all) Molecular Sequence Data PDZ domain MESH: Carrier Proteins Nerve Tissue Proteins [SDV.BC]Life Sciences [q-bio]/Cellular Biology AMPA receptor Biology Transfection Receptors N-Methyl-D-Aspartate Cell Line Ca2+/calmodulin-dependent protein kinase MESH: Synaptic Transmission MESH: Calcium-Calmodulin-Dependent Protein Kinases Animals Humans Amino Acid Sequence [SDV.BC] Life Sciences [q-bio]/Cellular Biology MESH: Receptors N-Methyl-D-Aspartate MESH: Molecular Sequence Data MESH: Humans MESH: Transfection Membrane Proteins MESH: Mitogen-Activated Protein Kinases MESH: Cell Line Rats MESH: p38 Mitogen-Activated Protein Kinases nervous system Calcium-Calmodulin-Dependent Protein Kinases Synapses Synaptic plasticity Calcium-Calmodulin-Dependent Protein Kinase Type 2 Carrier Proteins Neuroscience |
| Zdroj: | Neuron Neuron, Elsevier, 2004, 43 (4), pp.563-74. ⟨10.1016/j.neuron.2004.08.003⟩ |
| ISSN: | 0896-6273 |
| DOI: | 10.1016/j.neuron.2004.08.003 |
| Popis: | International audience; The synapse contains densely localized and interacting proteins that enable it to adapt to changing inputs. We describe a Ca2+-sensitive protein complex involved in the regulation of AMPA receptor synaptic plasticity. The complex is comprised of MUPPI, a multi-PDZ domain-containing protein; SynGAP, a synaptic GTPase-activating protein; and the Ca2+/calmodulin-dependent kinase CaMKII. In synapses of hippocampal neurons, SynGAP and CaMKII are brought together by direct physical interaction with the PDZ domains of MUPP1, and in this complex, SynGAP is phosphorylated. Ca2+CaM binding to CaMKII dissociates it from the MUPP1 complex, and Ca2+ entering via the NMDAR drives the dephosphorylation of SynGAP. Specific peptide-induced SynGAP dissociation from the MUPP1-CaMKII complex results in SynGAP dephosphorylation accompanied by P38 MAPK inactivation, potentiation of synaptic AMPA responses, and an increase in the number of AMPAR-containing clusters in hippocampal neuron synapses. siRNA-mediated SynGAP knockdown confirmed these results. These data implicate SynGAP in NMDAR- and CaMKII-dependent regulation of AMPAR trafficking. |
| Databáze: | OpenAIRE |
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