Phosphorylation of the AMPA receptor subunit GluA1 regulates clathrin-mediated receptor internalization
| Autor: | Isabella G. Schmidt, Edward B. Ziff, Seonil Kim, Jessica P. Roberts, Latika Khatri, Regina Célia Cussa Kubrusly, Anastasiya Zaytseva, Matheus F. Sathler |
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| Rok vydání: | 2021 |
| Předmět: |
biology
musculoskeletal neural and ocular physiology media_common.quotation_subject Long-Term Potentiation Endocytic cycle Fluorescence recovery after photobleaching Long-term potentiation Cell Biology AMPA receptor Hippocampus Clathrin Cell biology nervous system Synapses Synaptic plasticity biology.protein Phosphorylation Receptors AMPA Internalization Research Article media_common |
| Zdroj: | J Cell Sci |
| ISSN: | 1477-9137 0021-9533 |
| Popis: | Synaptic strength is altered during synaptic plasticity by controlling the number of AMPA receptors (AMPARs) at excitatory synapses. During long-term potentiation and synaptic upscaling, AMPARs are accumulated at synapses to increase synaptic strength. Neuronal activity leads to phosphorylation of AMPAR subunit GluA1 (also known as GRIA1) and subsequent elevation of GluA1 surface expression, either by an increase in receptor forward trafficking to the synaptic membrane or a decrease in receptor internalization. However, the molecular pathways underlying GluA1 phosphorylation-induced elevation of surface AMPAR expression are not completely understood. Here, we employ fluorescence recovery after photobleaching (FRAP) to reveal that phosphorylation of GluA1 serine 845 (S845) predominantly plays a role in receptor internalization, rather than forward trafficking, during synaptic plasticity. Notably, internalization of AMPARs depends upon the clathrin adaptor AP2, which recruits cargo proteins into endocytic clathrin-coated pits. In fact, we further reveal that an increase in GluA1 S845 phosphorylation upon two distinct forms of synaptic plasticity diminishes the binding of the AP2 adaptor, reducing internalization and resulting in elevation of GluA1 surface expression. We thus demonstrate a mechanism of GluA1 phosphorylation-regulated clathrin-mediated internalization of AMPARs. |
| Databáze: | OpenAIRE |
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