Regulated RalBP1 Binding to RalA and PSD-95 Controls AMPA Receptor Endocytosis and LTD
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Han-2009-Regulated RalBP1 Binding to RalA and PSD-95 Controls AMPA Receptor Endocytosis and LTD.pdf
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1.6 MB
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Author(s)
Han, Kihoon
Kim, Myoung-Hwan
Seeburg, Daniel P.
Seo, Jinsoo
Verpelli, Chiara
Han, Seungnam
Chung, Hye Sun
Ko, Jaewon
Lee, Hyun Woo
Kim, Karam
Date Issued
September 2009
Journal
PLoS Biology
Publisher
Public Library of Science
Citation
Han K, Kim M-H, Seeburg D, Seo J, Verpelli C, et al. (2009) Regulated RalBP1 Binding to RalA and PSD-95 Controls AMPA Receptor Endocytosis and LTD. PLoS Biol 7(9): e1000187. doi:10.1371/journal.pbio.1000187
Version
Final published version
Abstract
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.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
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DOI of Published Version
http://dx.doi.org/10.1371/journal.pbio.1000187
