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  • Activity-dependent synaptic GRIP1 accumulation drives synaptic scaling up in response to action potential blockade.

Activity-dependent synaptic GRIP1 accumulation drives synaptic scaling up in response to action potential blockade.

Proceedings of the National Academy of Sciences of the United States of America (2015-06-26)
Melanie A Gainey, Vedakumar Tatavarty, Marc Nahmani, Heather Lin, Gina G Turrigiano
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Glutamate Receptor 2 Antibody, extracellular, clone 6C4, clone 6C4, Chemicon®, from mouse
Sigma-Aldrich
Anti-Green Fluorescent Protein Antibody, Chemicon®, from rabbit