Activity-dependent synaptic GRIP1 accumulation drives synaptic scaling up in response to action potential blockade
| Autor: | Vedakumar Tatavarty, Heather Lin, Melanie A. Gainey, Marc Nahmani, Gina G. Turrigiano |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Patch-Clamp Techniques
Neural facilitation Action Potentials Nerve Tissue Proteins Tetrodotoxin Biology Homeostatic plasticity Synaptic augmentation Metaplasticity Animals Rats Long-Evans Receptors AMPA Microscopy Immunoelectron Cells Cultured Neurons Multidisciplinary Synaptic scaling Microscopy Confocal musculoskeletal neural and ocular physiology Intracellular Signaling Peptides and Proteins Excitatory Postsynaptic Potentials Synaptic fatigue nervous system PNAS Plus Animals Newborn Synaptic plasticity Synapses RNA Interference Carrier Proteins Synaptic tagging Neuroscience Protein Binding |
| Popis: | Synaptic scaling is a form of homeostatic plasticity that stabilizes neuronal firing in response to changes in synapse number and strength. Scaling up in response to action-potential blockade is accomplished through increased synaptic accumulation of GluA2-containing AMPA receptors (AMPAR), but the receptor trafficking steps that drive this process remain largely obscure. Here, we show that the AMPAR-binding protein glutamate receptor-interacting protein-1 (GRIP1) is essential for regulated synaptic AMPAR accumulation during scaling up. Synaptic abundance of GRIP1 was enhanced by activity deprivation, directly increasing synaptic GRIP1 abundance through overexpression increased the amplitude of AMPA miniature excitatory postsynaptic currents (mEPSCs), and shRNA-mediated GRIP1 knockdown prevented scaling up of AMPA mEPSCs. Furthermore, knockdown and replace experiments targeting either GRIP1 or GluA2 revealed that scaling up requires the interaction between GRIP1 and GluA2. Finally, GRIP1 synaptic accumulation during scaling up did not require GluA2 binding. Taken together, our data support a model in which activity-dependent trafficking of GRIP1 to synaptic sites drives the forward trafficking and enhanced synaptic accumulation of GluA2-containing AMPAR during synaptic scaling up. |
| Databáze: | OpenAIRE |
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