| GKAP orchestrates activity-dependent postsynaptic protein remodeling and homeostatic scaling. | |
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MedLine Citation:
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PMID: 23143515 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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How does chronic activity modulation lead to global remodeling of proteins at synapses and synaptic scaling? Here we report that guanylate kinase-associated protein (GKAP; also known as SAPAP), a scaffolding molecule linking NMDA receptor-PSD-95 to Shank-Homer complexes, acts in these processes. Overexcitation removes GKAP from synapses via the ubiquitin-proteasome system, whereas inactivity induces synaptic accumulation of GKAP in rat hippocampal neurons. Bidirectional changes in synaptic GKAP amounts are controlled by specific CaMKII isoforms coupled to different Ca(2+) channels. CaMKIIα activated by the NMDA receptor phosphorylates GKAP Ser54 to induce polyubiquitination of GKAP. In contrast, CaMKIIβ activation via L-type voltage-dependent calcium channels promotes GKAP recruitment by phosphorylating GKAP Ser340 and Ser384, which uncouples GKAP from myosin Va motor complex. Overexpressing GKAP turnover mutants not only hampers activity-dependent remodeling of PSD-95 and Shank but also blocks bidirectional synaptic scaling. Therefore, activity-dependent turnover of PSD proteins orchestrated by GKAP is critical for homeostatic plasticity. |
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Authors:
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Seung Min Shin; Nanyan Zhang; Jonathan Hansen; Nashaat Z Gerges; Daniel T S Pak; Morgan Sheng; Sang H Lee |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-11-11 |
Journal Detail:
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Title: Nature neuroscience Volume: - ISSN: 1546-1726 ISO Abbreviation: Nat. Neurosci. Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-12 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9809671 Medline TA: Nat Neurosci Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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