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

被引:154
作者
Huang, CC [1 ]
You, JL [1 ]
Wu, MY [1 ]
Hsu, KS [1 ]
机构
[1] Natl Cheng Kung Univ, Coll Med, Dept Pharmacol, Tainan 701, Taiwan
关键词
D O I
10.1074/jbc.M312868200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
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 betagamma-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.
引用
收藏
页码:12286 / 12292
页数:7
相关论文
共 51 条
[31]   Tyrosine dephosphorylation underlies DHPG-induced LTD [J].
Moult, PR ;
Schnabel, R ;
Kilpatrick, IC ;
Bashir, ZI ;
Collingridge, GL .
NEUROPHARMACOLOGY, 2002, 43 (02) :175-180
[32]   The group I mGlu receptor agonist DHPG induces a novel form of LTD in the CA1 region of the hippocampus [J].
Palmer, MJ ;
Irving, AJ ;
Seabrook, GR ;
Jane, DE ;
Collingridge, GL .
NEUROPHARMACOLOGY, 1997, 36 (11-12) :1517-1532
[33]   Activation of mGlu receptors induces LTD without affecting postsynaptic sensitivity of CA1 neurons in rat hippocampal slices [J].
Rammes, G ;
Palmer, M ;
Eder, M ;
Dodt, HU ;
Zieglgänsberger, W ;
Collingridge, GL .
JOURNAL OF PHYSIOLOGY-LONDON, 2003, 546 (02) :455-460
[34]  
Rush AM, 2002, J NEUROSCI, V22, P6121
[35]  
Sawada Y, 2001, J CELL SCI, V114, P1221
[36]   An investigation into signal transduction mechanisms involved in DHPG-induced LTD in the CA1 region of the hippocampus [J].
Schnabel, R ;
Kilpatrick, IC ;
Collingridge, GL .
NEUROPHARMACOLOGY, 1999, 38 (10) :1585-1596
[37]   A CaMKII inhibitor, KN-62, facilitates DHPG-induced LTD in the CA1 region of the hippocampus [J].
Schnabel, R ;
Palmer, MJ ;
Kilpatrick, IC ;
Collingridge, GL .
NEUROPHARMACOLOGY, 1999, 38 (04) :605-608
[38]   Protein phosphatase inhibitors facilitate DHPG-induced LTD in the CA1 region of the hippocampus [J].
Schnabel, R ;
Kilpatrick, IC ;
Collingridge, GL .
BRITISH JOURNAL OF PHARMACOLOGY, 2001, 132 (05) :1095-1101
[39]   Heterotrimeric G-protein βγ-dimers in growth and differentiation [J].
Schwindinger, WF ;
Robishaw, JD .
ONCOGENE, 2001, 20 (13) :1653-1660
[40]   Receptor isoforms mediate opposing proliferative effects through Gβγ-activated p38 or Akt pathways [J].
Sellers, LA ;
Alderton, F ;
Carruthers, AM ;
Schindler, M ;
Humphrey, PPA .
MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (16) :5974-5985