Regulated RalBP1 binding to RalA and PSD-95 controls AMPA receptor endocytosis and LTD

Kihoon Han, Myoung Hwan Kim, Daniel Seeburg, Jinsoo Seo, Chiara Verpelli, Seungnam Han, Sun Chung Hye, Jaewon Ko, Woo Lee Hyun, Karam Kim, Do Heo Won, Tobias Meyer, Hyun Kim, Carlo Sala, Se Young Choi, Morgan Sheng, Eunjoon Kim

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)

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.

Original languageEnglish
Article numbere1000187
JournalPLoS biology
Volume7
Issue number9
DOIs
Publication statusPublished - 2009

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

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