GKAP/SAPAP orchestrates activity-dependent postsynaptic protein remodeling and homeostatic scaling
How does chronic activity modulation lead to global remodeling of proteins at synapses and synaptic scaling? Here we report a role of guanylate-kinase-associated-protein (GKAP; also known as SAPAP), a scaffolding molecule linking NMDA receptor-PSD-95 to Shank-Homer complexes, in these processes. Ove...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3804128/ https://www.ncbi.nlm.nih.gov/pubmed/23143515 http://dx.doi.org/10.1038/nn.3259 |
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author | Shin, Seung Min Zhang, Nanyan Hansen, Jonathan Gerges, Nashaat Z. Pak, Daniel T.S. Sheng, Morgan Lee, Sang H. |
author_facet | Shin, Seung Min Zhang, Nanyan Hansen, Jonathan Gerges, Nashaat Z. Pak, Daniel T.S. Sheng, Morgan Lee, Sang H. |
author_sort | Shin, Seung Min |
collection | PubMed |
description | How does chronic activity modulation lead to global remodeling of proteins at synapses and synaptic scaling? Here we report a role of guanylate-kinase-associated-protein (GKAP; also known as SAPAP), a scaffolding molecule linking NMDA receptor-PSD-95 to Shank-Homer complexes, in these processes. Over-excitation removes GKAP from synapses via ubiquitin-proteasome system, while inactivity induces synaptic accumulation of GKAP in rat hippocampal neurons. The bi-directional changes of synaptic GKAP levels are controlled by specific CaMKII isoforms coupled to different Ca(2+) channels. α-CaMKII activated by NMDA receptor phosphorylates Serine-54 of GKAP to induce poly-ubiquitination of GKAP. In contrast, β-CaMKII activation via L-type voltage-dependent calcium channel promotes GKAP recruitment by phosphorylating Serine-340 and Serine-384 residues, which uncouples GKAP from MyoVa motor complex. Remarkably, overexpressing GKAP turnover mutants not only hampers activity-dependent remodeling of PSD-95 and Shank but also blocks bi-directional synaptic scaling. Therefore, activity-dependent turnover of PSD proteins orchestrated by GKAP is critical for homeostatic plasticity. |
format | Online Article Text |
id | pubmed-3804128 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
record_format | MEDLINE/PubMed |
spelling | pubmed-38041282013-10-21 GKAP/SAPAP orchestrates activity-dependent postsynaptic protein remodeling and homeostatic scaling Shin, Seung Min Zhang, Nanyan Hansen, Jonathan Gerges, Nashaat Z. Pak, Daniel T.S. Sheng, Morgan Lee, Sang H. Nat Neurosci Article How does chronic activity modulation lead to global remodeling of proteins at synapses and synaptic scaling? Here we report a role of guanylate-kinase-associated-protein (GKAP; also known as SAPAP), a scaffolding molecule linking NMDA receptor-PSD-95 to Shank-Homer complexes, in these processes. Over-excitation removes GKAP from synapses via ubiquitin-proteasome system, while inactivity induces synaptic accumulation of GKAP in rat hippocampal neurons. The bi-directional changes of synaptic GKAP levels are controlled by specific CaMKII isoforms coupled to different Ca(2+) channels. α-CaMKII activated by NMDA receptor phosphorylates Serine-54 of GKAP to induce poly-ubiquitination of GKAP. In contrast, β-CaMKII activation via L-type voltage-dependent calcium channel promotes GKAP recruitment by phosphorylating Serine-340 and Serine-384 residues, which uncouples GKAP from MyoVa motor complex. Remarkably, overexpressing GKAP turnover mutants not only hampers activity-dependent remodeling of PSD-95 and Shank but also blocks bi-directional synaptic scaling. Therefore, activity-dependent turnover of PSD proteins orchestrated by GKAP is critical for homeostatic plasticity. 2012-11-11 2012-12 /pmc/articles/PMC3804128/ /pubmed/23143515 http://dx.doi.org/10.1038/nn.3259 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Shin, Seung Min Zhang, Nanyan Hansen, Jonathan Gerges, Nashaat Z. Pak, Daniel T.S. Sheng, Morgan Lee, Sang H. GKAP/SAPAP orchestrates activity-dependent postsynaptic protein remodeling and homeostatic scaling |
title | GKAP/SAPAP orchestrates activity-dependent postsynaptic protein remodeling and homeostatic scaling |
title_full | GKAP/SAPAP orchestrates activity-dependent postsynaptic protein remodeling and homeostatic scaling |
title_fullStr | GKAP/SAPAP orchestrates activity-dependent postsynaptic protein remodeling and homeostatic scaling |
title_full_unstemmed | GKAP/SAPAP orchestrates activity-dependent postsynaptic protein remodeling and homeostatic scaling |
title_short | GKAP/SAPAP orchestrates activity-dependent postsynaptic protein remodeling and homeostatic scaling |
title_sort | gkap/sapap orchestrates activity-dependent postsynaptic protein remodeling and homeostatic scaling |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3804128/ https://www.ncbi.nlm.nih.gov/pubmed/23143515 http://dx.doi.org/10.1038/nn.3259 |
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