Plk2 attachment to NSF induces homeostatic removal of GluA2 during chronic overexcitation

被引:57
作者
Evers, Danielle M. [1 ]
Matta, Jose A. [1 ,2 ]
Hoe, Hyang-Sook [3 ]
Zarkowsky, Devin [1 ]
Lee, Sang Hyoung [4 ]
Isaac, John T. [2 ]
Pak, Daniel T. S. [1 ]
机构
[1] Georgetown Univ, Med Ctr, Dept Pharmacol, Washington, DC 20007 USA
[2] NIGMS, NIH, Bethesda, MD USA
[3] Georgetown Univ, Dept Neurosci, Washington, DC 20007 USA
[4] Med Coll Wisconsin, Dept Pharmacol, Milwaukee, WI 53226 USA
基金
美国国家卫生研究院;
关键词
AMPA RECEPTOR TRAFFICKING; ETHYLMALEIMIDE-SENSITIVE FACTOR; DOMAIN-CONTAINING PROTEINS; LONG-TERM POTENTIATION; POLO-LIKE KINASE; HIPPOCAMPAL-NEURONS; SYNAPTIC-TRANSMISSION; SURFACE EXPRESSION; SUBUNIT COMPOSITION; BINDING PROTEIN;
D O I
10.1038/nn.2624
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Trafficking of AMPA receptors (AMPARs) is important for many forms of synaptic plasticity. However, the link between activity and resulting synaptic alterations is not fully understood. We identified a direct interaction between N-ethylmaleimide-sensitive fusion protein (NSF), an ATPase involved in membrane fusion events and stabilization of surface AMPARs, and Polo-like kinase-2 (Plk2), an activity-inducible kinase that homeostatically decreases excitatory synapse number and strength. Plk2 disrupted the interaction of NSF with the GluA2 subunit of AMPARs, promoting extensive loss of surface GluA2 in rat hippocampal neurons, greater association of GluA2 with adaptor proteins PICK1 and GRIP1, and decreased synaptic AMPAR current. Plk2 engagement of NSF, but not Plk2 kinase activity, was required for this mechanism and occurred through a motif in the Plk2 protein that was independent of the canonical polo box interaction sites. These data reveal that heightened synaptic activity, acting through Plk2, leads to homeostatic decreases in surface AMPAR expression via the direct dissociation of NSF from GluA2.
引用
收藏
页码:1199 / 1207
页数:9
相关论文
共 50 条
[1]   Regulation of Postsynaptic RapGAP SPAR by Polo-like Kinase 2 and the SCFβ-TRCP Ubiquitin Ligase in Hippocampal Neurons [J].
Ang, Xiaolu L. ;
Seeburg, Daniel P. ;
Sheng, Morgan ;
Harper, J. Wade .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (43) :29424-29432
[2]   NSF interaction is important for direct insertion of GluR2 at synaptic sites [J].
Beretta, F ;
Sala, C ;
Saglietti, L ;
Hirling, H ;
Sheng, M ;
Passafaro, M .
MOLECULAR AND CELLULAR NEUROSCIENCE, 2005, 28 (04) :650-660
[3]   Endocytosis and recycling of AMPA receptors lacking GIuR2/3 [J].
Biou, Virginie ;
Bhattacharyya, Samarjit ;
Malenka, Robert C. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (03) :1038-1043
[4]   Differential roles for NSF and GRIP/ABP in AMPA receptor cycling [J].
Braithwaite, SP ;
Xia, HH ;
Malenka, RC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (10) :7096-7101
[5]  
Chung HJ, 2000, J NEUROSCI, V20, P7258
[6]   PDZ proteins interacting with C-terminal GluR2/3 are involved in a PKC-dependent regulation of AMPA receptors at hippocampal synapses [J].
Daw, MI ;
Chittajallu, R ;
Bortolotto, ZA ;
Dev, KK ;
Duprat, F ;
Henley, JM ;
Collingridge, GL ;
Isaac, JTR .
NEURON, 2000, 28 (03) :873-886
[7]  
DeSouza S, 2002, J NEUROSCI, V22, P3493
[8]   Characterization, expression, and distribution of GRIP protein [J].
Dong, HL ;
Zhang, PS ;
Liao, DZ ;
Huganir, RL .
MOLECULAR AND FUNCTIONAL DIVERSITY OF ION CHANNELS AND RECEPTORS, 1999, 868 :535-540
[9]   The molecular basis for phosphodependent substrate targeting and regulation of Plks by the Polo-box domain [J].
Elia, AEH ;
Rellos, P ;
Haire, LF ;
Chao, JW ;
Ivins, FJ ;
Hoepker, K ;
Mohammad, D ;
Cantley, LC ;
Smerdon, SJ ;
Yaffe, MB .
CELL, 2003, 115 (01) :83-95
[10]   Association of polo-like kinase with α-, β- and γ-tubulins in a stable complex [J].
Feng, Y ;
Hodge, DR ;
Palmieri, G ;
Chase, DL ;
Longo, DL ;
Ferris, DK .
BIOCHEMICAL JOURNAL, 1999, 339 :435-442