Translational control of mGluR-dependent long-term depression and object-place learning by eIF2α

被引：154

作者：

Di Prisco, Gonzalo Viana ^{[1
,2
]}

Huang, Wei ^{[1
,2
]}

Buffington, Shelly A. ^{[1
,2
]}

Hsu, Chih-Chun ^{[1
,2
]}

Bonnen, Penelope E. ^{[3
]}

Placzek, AndonN ^{[1
]}

Sidrauski, Carmela ^{[4
]}

Krnjevic, Kresimir ^{[5
]}

Kaufman, Randal J. ^{[6
]}

Walter, Peter ^{[4
]}

Costa-Mattioli, Mauro ^{[1
,2
]}

机构：

[1] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA

[2] Baylor Coll Med, Memory & Brain Res Ctr, Houston, TX 77030 USA

[3] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[4] Univ Calif San Francisco, Howard Hughes Med Inst, Dept Biochem & Biophys, San Francisco, CA USA

[5] McGill Univ, Dept Physiol, Montreal, PQ, Canada

[6] Sanford Burnham Med Res Inst, Ctr Neurosci Aging & Stem Cell Res, La Jolla, CA USA

来源：

NATURE NEUROSCIENCE | 2014年 / 17卷 / 08期

基金：

美国国家卫生研究院;

关键词：

METABOTROPIC GLUTAMATE-RECEPTOR; MENTAL-RETARDATION PROTEIN; SYNAPTIC PLASTICITY; IN-VIVO; GENERAL TRANSLATION; LTD; MEMORY; HIPPOCAMPUS; MECHANISMS; ACTIVATION;

D O I：

10.1038/nn.3754

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

At hippocampal synapses, activation of group I metabotropic glutamate receptors (mGluRs) induces long-term depression (LTD), which requires new protein synthesis. However, the underlying mechanism remains elusive. Here we describe the translational program that underlies mGluR-LTD and identify the translation factor eIF2 alpha as its master effector. Genetically reducing eIF2 alpha phosphorylation, or specifically blocking the translation controlled by eIF2 alpha phosphorylation, prevented mGluR-LTD and the internalization of surface AMPA receptors (AMPARs). Conversely, direct phosphorylation of eIF2 alpha, bypassing mGluR activation, triggered a sustained LTD and removal of surface AMPARs. Combining polysome profiling and RNA sequencing, we identified the mRNAs translationally upregulated during mGluR-LTD. Translation of one of these mRNAs, oligophrenin-1, mediates the LTD induced by eIF2 alpha phosphorylation. Mice deficient in phospho-eIF2 alpha-mediated translation are impaired in object-place learning, a behavioral task that induces hippocampal mGluR-LTD in vivo. Our findings identify a new model of mGluR-LTD, which promises to be of value in the treatment of mGluR-LTD-linked cognitive disorders.

引用

页码：1073 / 1082

页数：10

共 37 条

[1] Mutations causing syndromic autism define an axis of synaptic pathophysiology [J].

Auerbach, Benjamin D. ;

Osterweil, Emily K. ;

Bear, Mark F. .

NATURE, 2011, 480 (7375) :63-U222

[2] Loss of Tsc1 In Vivo Impairs Hippocampal mGluR-LTD and Increases Excitatory Synaptic Function [J].

Bateup, Helen S. ;

Takasaki, Kevin T. ;

Saulnier, Jessica L. ;

Denefrio, Cassandra L. ;

Sabatini, Bernardo L. .

JOURNAL OF NEUROSCIENCE, 2011, 31 (24) :8862-8869

[3] A selective inhibitor-of eIF2α dephosphorylation protects cells from ER stress [J].

Boyce, M ;

Bryant, KF ;

Jousse, C ;

Long, K ;

Harding, HP ;

Scheuner, D ;

Kaufman, RJ ;

Ma, DW ;

Coen, DM ;

Ron, D ;

Yuan, JY .

SCIENCE, 2005, 307 (5711) :935-939

[4] Long-term depression in the CNS [J].

Collingridge, Graham L. ;

Peineau, Stephane ;

Howland, John G. ;

Wang, Yu Tian .

NATURE REVIEWS NEUROSCIENCE, 2010, 11 (07) :459-473

[5] Translational control of hippocampal synaptic plasticity and memory by the eIF2α kinase GCN2 [J].

Costa-Mattioli, M ;

Gobert, D ;

Harding, H ;

Herdy, B ;

Azzi, M ;

Bruno, M ;

Bidinosti, M ;

Ben Mamou, C ;

Marcinkiewicz, E ;

Yoshida, M ;

Imataka, H ;

Cuello, AC ;

Seidah, N ;

Sossin, W ;

Lacaille, JC ;

Ron, D ;

Nader, K ;

Sonenberg, N .

NATURE, 2005, 436 (7054) :1166-1170

[6] eIF2α phosphorylation bidirectionally regulates the switch from short- to long-term synaptic plasticity and memory [J].

Costa-Mattioli, Mauro ;

Gobert, Delphine ;

Stern, Elad ;

Gamache, Karine ;

Colina, Rodney ;

Cuello, Claudio ;

Sossin, Wayne ;

Kaufman, Randal ;

Pelletier, Jerrf ;

Rosenblum, Kobi ;

Krnjevic, Kresimir ;

Lacaille, Jean-Claude ;

Nader, Karim ;

Sonenberg, Nahum .

CELL, 2007, 129 (01) :195-206

[7] Translational Control of Long-Lasting Synaptic Plasticity and Memory [J].

Costa-Mattioli, Mauro ;

Sossin, Wayne S. ;

Klann, Eric ;

Sonenberg, Nahum .

NEURON, 2009, 61 (01) :10-26

[8] Characterization of the role of microtubule-associated protein 1B in metabotropic glutamate receptor-mediated endocytosis of AMPA receptors in hippocampus [J].

Davidkova, Genoveva ;

Carroll, Reed C. .

JOURNAL OF NEUROSCIENCE, 2007, 27 (48) :13273-13278

[9] Gene-specific regulation by general translation factors [J].

Dever, TE .

CELL, 2002, 108 (04) :545-556

[10] Metabotropic Glutamate Receptor-Mediated Long-Term Depression: Molecular Mechanisms [J].

Gladding, Clare M. ;

Fitzjohn, Stephen M. ;

Molnar, Elek .

PHARMACOLOGICAL REVIEWS, 2009, 61 (04) :395-412

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