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

研究成果: Article同行評審

140 引文 斯高帕斯(Scopus)

摘要

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.

原文English
頁(從 - 到)12286-12292
頁數7
期刊Journal of Biological Chemistry
279
發行號13
DOIs
出版狀態Published - 2004 三月 26

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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