mTOR signaling: At the crossroads of plasticity, memory and disease

被引:859
作者
Hoeffer, Charles A. [1 ]
Klann, Eric [1 ]
机构
[1] NYU, Ctr Neural Sci, New York, NY 10003 USA
关键词
LONG-TERM POTENTIATION; RAPAMYCIN-SENSITIVE MANNER; SYNAPTIC PLASTICITY; MAMMALIAN TARGET; PROTEIN-SYNTHESIS; TRANSLATIONAL CONTROL; MICE LACKING; COMPLEX-FORMATION; KINASE-ACTIVITY; CYCLOSPORINE-A;
D O I
10.1016/j.tins.2009.11.003
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Mammalian target of rapamycin (mTOR) is a protein kinase involved in translation control and long-lasting synaptic plasticity. mTOR functions as the central component of two multi-protein signaling complexes, mTORC1 and mTORC2, which can be distinguished from each other based on their unique compositions and substrates. Although the majority of evidence linking mTOR function to synaptic plasticity comes from studies utilizing rapamycin, studies in genetically modified mice also suggest that mTOR couples receptors to the translation machinery for establishing long-lasting synaptic changes that are the basis for higher order brain function, including long-term memory. Finally, perturbation of the mTOR signaling cascade appears to be a common pathophysiological feature of human neurological disorders, including mental retardation syndromes and autism spectrum disorders.
引用
收藏
页码:67 / 75
页数:9
相关论文
共 113 条
[1]   Rapamycin regulates the phosphorylation of rictor [J].
Akcakanat, Argun ;
Singh, Gopal ;
Hung, Mien-Chie ;
Meric-Bernstam, Funda .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2007, 362 (02) :330-333
[2]   Removal of S6K1 and S6K2 leads to divergent alterations in learning, memory, and synaptic plasticity [J].
Antion, Marcia D. ;
Merhav, Maayan ;
Hoeffer, Charles A. ;
Reis, Gerald ;
Kozma, Sara C. ;
Thomas, George ;
Schuman, Erin M. ;
Rosenblum, Kobi ;
Klann, Eric .
LEARNING & MEMORY, 2008, 15 (01) :29-38
[3]   mGluR-dependent long-term depression is associated with increased phosphorylation of S6 and synthesis of elongation factor 1A but remains expressed in S6K-deficient mice [J].
Antion, Marcia D. ;
Hou, Lingfei ;
Wong, Helen ;
Hoeffer, Charles A. ;
Klann, Eric .
MOLECULAR AND CELLULAR BIOLOGY, 2008, 28 (09) :2996-3007
[4]   From mRNP trafficking to spine dysmorphogenesis: The roots of fragile X syndrome [J].
Bagni, C ;
Greenough, WT .
NATURE REVIEWS NEUROSCIENCE, 2005, 6 (05) :376-387
[5]   Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38 [J].
Bai, Xiaochun ;
Ma, Dongzhu ;
Liu, Anling ;
Shen, Xiaoyun ;
Wang, Qiming J. ;
Liu, Yongjian ;
Jiang, Yu .
SCIENCE, 2007, 318 (5852) :977-980
[6]   Characterization of the FKBP•Rapamycin•FRB ternary complex [J].
Banaszynski, LA ;
Liu, CW ;
Wandless, TJ .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2005, 127 (13) :4715-4721
[7]   Behavioral alterations in mice lacking the translation repressor 4E-BP2 [J].
Banko, Jessica L. ;
Merhav, Maayan ;
Stern, Elad ;
Sonenberg, Nahum ;
Rosenblum, Kobi ;
Klann, Eric .
NEUROBIOLOGY OF LEARNING AND MEMORY, 2007, 87 (02) :248-256
[8]   NMDA receptor activation results in PKA- and ERK-dependent Mnk1 activation and increased eIF4E phosphorylation in hippocampal area CA1 [J].
Banko, JL ;
Hou, LF ;
Klann, E .
JOURNAL OF NEUROCHEMISTRY, 2004, 91 (02) :462-470
[9]   Regulation of eukaryotic initiation factor 4E by converging signaling pathways during metabotropic glutamate receptor-dependent long-term depression [J].
Banko, JL ;
Hou, LF ;
Poulin, F ;
Sonenberg, N ;
Klann, E .
JOURNAL OF NEUROSCIENCE, 2006, 26 (08) :2167-2173
[10]   The translation repressor 4E-BP2 is critical for eIF4F complex formation, synaptic plasticity, and memory in the hippocampus [J].
Banko, JL ;
Poulin, F ;
Hou, LF ;
DeMaria, CT ;
Sonenberg, N ;
Klann, E .
JOURNAL OF NEUROSCIENCE, 2005, 25 (42) :9581-9590