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Regulated RalBP1 Binding to RalA and PSD-95 Controls AMPA Receptor Endocytosis and LTD

Long-term depression (LTD) is a long-lasting activity-dependent decrease in synaptic strength. NMDA receptor (NMDAR)–dependent LTD, an extensively studied form of LTD, involves the endocytosis of AMPA receptors (AMPARs) via protein dephosphorylation, but the underlying mechanism has remained unclear...

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Autores principales: Han, Kihoon, Kim, Myoung-Hwan, Seeburg, Daniel, Seo, Jinsoo, Verpelli, Chiara, Han, Seungnam, Chung, Hye Sun, Ko, Jaewon, Lee, Hyun Woo, Kim, Karam, Heo, Won Do, Meyer, Tobias, Kim, Hyun, Sala, Carlo, Choi, Se-Young, Sheng, Morgan, Kim, Eunjoon
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730530/
https://www.ncbi.nlm.nih.gov/pubmed/19823667
http://dx.doi.org/10.1371/journal.pbio.1000187
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author Han, Kihoon
Kim, Myoung-Hwan
Seeburg, Daniel
Seo, Jinsoo
Verpelli, Chiara
Han, Seungnam
Chung, Hye Sun
Ko, Jaewon
Lee, Hyun Woo
Kim, Karam
Heo, Won Do
Meyer, Tobias
Kim, Hyun
Sala, Carlo
Choi, Se-Young
Sheng, Morgan
Kim, Eunjoon
author_facet Han, Kihoon
Kim, Myoung-Hwan
Seeburg, Daniel
Seo, Jinsoo
Verpelli, Chiara
Han, Seungnam
Chung, Hye Sun
Ko, Jaewon
Lee, Hyun Woo
Kim, Karam
Heo, Won Do
Meyer, Tobias
Kim, Hyun
Sala, Carlo
Choi, Se-Young
Sheng, Morgan
Kim, Eunjoon
author_sort Han, Kihoon
collection PubMed
description Long-term depression (LTD) is a long-lasting activity-dependent decrease in synaptic strength. NMDA receptor (NMDAR)–dependent LTD, an extensively studied form of LTD, involves the endocytosis of AMPA receptors (AMPARs) via protein dephosphorylation, but the underlying mechanism has remained unclear. We show here that a regulated interaction of the endocytic adaptor RalBP1 with two synaptic proteins, the small GTPase RalA and the postsynaptic scaffolding protein PSD-95, controls NMDAR-dependent AMPAR endocytosis during LTD. NMDAR activation stimulates RalA, which binds and translocates widespread RalBP1 to synapses. In addition, NMDAR activation dephosphorylates RalBP1, promoting the interaction of RalBP1 with PSD-95. These two regulated interactions are required for NMDAR-dependent AMPAR endocytosis and LTD and are sufficient to induce AMPAR endocytosis in the absence of NMDAR activation. RalA in the basal state, however, maintains surface AMPARs. We propose that NMDAR activation brings RalBP1 close to PSD-95 to promote the interaction of RalBP1-associated endocytic proteins with PSD-95-associated AMPARs. This suggests that scaffolding proteins at specialized cellular junctions can switch their function from maintenance to endocytosis of interacting membrane proteins in a regulated manner.
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spelling pubmed-27305302009-09-08 Regulated RalBP1 Binding to RalA and PSD-95 Controls AMPA Receptor Endocytosis and LTD Han, Kihoon Kim, Myoung-Hwan Seeburg, Daniel Seo, Jinsoo Verpelli, Chiara Han, Seungnam Chung, Hye Sun Ko, Jaewon Lee, Hyun Woo Kim, Karam Heo, Won Do Meyer, Tobias Kim, Hyun Sala, Carlo Choi, Se-Young Sheng, Morgan Kim, Eunjoon PLoS Biol Research Article Long-term depression (LTD) is a long-lasting activity-dependent decrease in synaptic strength. NMDA receptor (NMDAR)–dependent LTD, an extensively studied form of LTD, involves the endocytosis of AMPA receptors (AMPARs) via protein dephosphorylation, but the underlying mechanism has remained unclear. We show here that a regulated interaction of the endocytic adaptor RalBP1 with two synaptic proteins, the small GTPase RalA and the postsynaptic scaffolding protein PSD-95, controls NMDAR-dependent AMPAR endocytosis during LTD. NMDAR activation stimulates RalA, which binds and translocates widespread RalBP1 to synapses. In addition, NMDAR activation dephosphorylates RalBP1, promoting the interaction of RalBP1 with PSD-95. These two regulated interactions are required for NMDAR-dependent AMPAR endocytosis and LTD and are sufficient to induce AMPAR endocytosis in the absence of NMDAR activation. RalA in the basal state, however, maintains surface AMPARs. We propose that NMDAR activation brings RalBP1 close to PSD-95 to promote the interaction of RalBP1-associated endocytic proteins with PSD-95-associated AMPARs. This suggests that scaffolding proteins at specialized cellular junctions can switch their function from maintenance to endocytosis of interacting membrane proteins in a regulated manner. Public Library of Science 2009-09-08 /pmc/articles/PMC2730530/ /pubmed/19823667 http://dx.doi.org/10.1371/journal.pbio.1000187 Text en Han et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Han, Kihoon
Kim, Myoung-Hwan
Seeburg, Daniel
Seo, Jinsoo
Verpelli, Chiara
Han, Seungnam
Chung, Hye Sun
Ko, Jaewon
Lee, Hyun Woo
Kim, Karam
Heo, Won Do
Meyer, Tobias
Kim, Hyun
Sala, Carlo
Choi, Se-Young
Sheng, Morgan
Kim, Eunjoon
Regulated RalBP1 Binding to RalA and PSD-95 Controls AMPA Receptor Endocytosis and LTD
title Regulated RalBP1 Binding to RalA and PSD-95 Controls AMPA Receptor Endocytosis and LTD
title_full Regulated RalBP1 Binding to RalA and PSD-95 Controls AMPA Receptor Endocytosis and LTD
title_fullStr Regulated RalBP1 Binding to RalA and PSD-95 Controls AMPA Receptor Endocytosis and LTD
title_full_unstemmed Regulated RalBP1 Binding to RalA and PSD-95 Controls AMPA Receptor Endocytosis and LTD
title_short Regulated RalBP1 Binding to RalA and PSD-95 Controls AMPA Receptor Endocytosis and LTD
title_sort regulated ralbp1 binding to rala and psd-95 controls ampa receptor endocytosis and ltd
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730530/
https://www.ncbi.nlm.nih.gov/pubmed/19823667
http://dx.doi.org/10.1371/journal.pbio.1000187
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