Rap1-induced p38 mitogen-activated protein kinase activation facilitates AMPA receptor trafficking via the GDI·Rab5 complex: Potential role in (S)-3,5-dihydroxyphenylglycine-induced long term depression

Chiung Chun Huang, Jia Lin You, Mei Ying Wu, Kuei-Sen Hsu

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139 Citations (Scopus)

Abstract

Recent evidence has emphasized the importance of p38 mitogen-activated protein kinase (MAPK) in the induction of metabotropic glutamate receptor (mGluR)-dependent long term depression (LTD) at hippocampal CA3-CA1 synapses. However, the cascade responsible of mGluR to activate p38 MAPK and the signaling pathway immediately downstream from it to induce synaptic depression is poorly understood. Here, we show that transient activation of group I mGluR with the selective agonist (S)-3,5-dihydroxyphenylglycine (DHPG) activates p38 MAPK through G protein βγ-subunit, small GTPase Rap1, and MAPK kinase 3/6 (MKK3/6), thus resulting in mGluR5-dependent LTD. Furthermore, our data clearly show that an accelerating AMPA receptor endocytosis by stimulating the formation of guanyl nucleotide dissociation inhibitor-Rab5 complex is a potential downstream processing of p38 MAPK activation to mediate DHPG-LTD. These results suggest an important role for Rap1-MKK3/6-p38 MAPK pathway in the induction of mGluR-dependent LTD by directly coupling to receptor trafficking machineries to facilitate the loss of synaptic AMPA receptors.

Original languageEnglish
Pages (from-to)12286-12292
Number of pages7
JournalJournal of Biological Chemistry
Volume279
Issue number13
DOIs
Publication statusPublished - 2004 Mar 26

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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