Rap2-JNK removes synaptic AMPA receptors during depotentiation

Yinghua Zhu, Daniel Pak, Yi Qin, Stefanie G. Mccormack, Myung J. Kim, Joel P. Baumgart, Vanisree Velamoor, Yves P. Auberson, Pavel Osten, Linda Van Aelst, Morgan Sheng, J. Julius Zhu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

159 Scopus citations

Abstract

The related small GTPases Ras and Rap1 are important for signaling synaptic AMPA receptor (-R) trafficking during long-term potentiation (LTP) and long-term depression (LTD), respectively. Rap2, which shares 60% identity to Rap1, is present at excitatory synapses, but its functional role is unknown. Here, we report that Rap2 activity, stimulated by NR2A-containing NMDA-R activation, depresses AMPA-R-mediated synaptic transmission via activation of JNK rather than Erk1/2 or p38 MAPK. Moreover, Rap2 controls synaptic removal of AMPA-Rs with long cytoplasmic termini during depotentiation. Thus, Rap2-JNK pathway, which opposes the action of the NR2A-containing NMDA-R-stimulated Ras-ERK1/2 signaling and complements the NR2B-containing NMDA-R-stimulated Rap1-p38 MAPK signaling, channels the specific signaling for depotentiating central synapses.

Original languageEnglish (US)
Pages (from-to)905-916
Number of pages12
JournalNeuron
Volume46
Issue number6
DOIs
StatePublished - Jun 16 2005

ASJC Scopus subject areas

  • Neuroscience(all)

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