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 language | English (US) |
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Pages (from-to) | 905-916 |
Number of pages | 12 |
Journal | Neuron |
Volume | 46 |
Issue number | 6 |
DOIs | |
State | Published - Jun 16 2005 |
Funding
We thank Drs. John Lawrence, Ian Macara, and Robert Malinow and members of the Zhu laboratory for helpful comments and discussions; Drs. Johannes Bos, José Esteban, and Josh Huang for RalGDS, pCITE-GFP, and dsRed-MST-B constructs; Dr. Brydon Bennett (Signal Pharmaceuticals Inc.) for gift of SP600125. This study is supported in part by the NIH and Whitehall Foundation. S.G.M. receives an NIH Predoctoral Training Fellowship, M.S. is an investigator of Howard Hughes Medical Institute, and J.J.Z. is an Alfred P. Sloan Fellow.
ASJC Scopus subject areas
- General Neuroscience