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
[41]   Upstream and downstream of mTOR [J].
Hay, N ;
Sonenberg, N .
GENES & DEVELOPMENT, 2004, 18 (16) :1926-1945
[42]   Increasing knowledge of PTEN germline mutations:: Two additional patients with autism and macrocephaly [J].
Herman, Gail E. ;
Butter, Eric ;
Enrile, Benedicta ;
Pastore, Matthew ;
Prior, Thomas W. ;
Sommer, Annemarie .
AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2007, 143A (06) :589-593
[43]   Removal of FKBP12 Enhances mTOR-Raptor Interactions, LTP, Memory, and Perseverative/Repetitive Behavior [J].
Hoeffer, Charles A. ;
Tang, Wei ;
Wong, Helen ;
Santillan, Arturo ;
Patterson, Richard J. ;
Martinez, Luis A. ;
Tejada-Simon, Maria V. ;
Paylor, Richard ;
Hamilton, Susan L. ;
Klann, Eric .
NEURON, 2008, 60 (05) :832-845
[44]   Identification of S6 kinase 1 as a novel mammalian target of rapamycin (mTOR)-phosphorylating kinase [J].
Holz, MK ;
Blenis, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (28) :26089-26093
[45]   Activation of the phosphoinositide 3-kinase-akt-mammalian target of rapamycin signaling pathway is required for metabotropic glutamate receptor-dependent long-term depression [J].
Hou, LF ;
Klann, E .
JOURNAL OF NEUROSCIENCE, 2004, 24 (28) :6352-6361
[46]   Dynamic translational and proteasomal regulation of fragile X mental retardation protein controls mGluR-dependent long-term depression [J].
Hou, Lingfei ;
Antion, Marcia D. ;
Hu, Daoying ;
Spencer, Corinne M. ;
Paylor, Richard ;
Klann, Eric .
NEURON, 2006, 51 (04) :441-454
[47]   A complex interplay between Akt, TSC2 and the two mTOR complexes [J].
Huang, Jingxiang ;
Manning, Brendan D. .
BIOCHEMICAL SOCIETY TRANSACTIONS, 2009, 37 :217-222
[48]   Altered synaptic plasticity in a mouse model of fragile X mental retardation [J].
Huber, KM ;
Gallagher, SM ;
Warren, ST ;
Bear, MF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (11) :7746-7750
[49]   Chemical induction of mGluR5-and protein synthesis-dependent long-term depression in hippocampal area CA1 [J].
Huber, KM ;
Roder, JC ;
Bear, MF .
JOURNAL OF NEUROPHYSIOLOGY, 2001, 86 (01) :321-325
[50]   What controls TOR? [J].
Jacinto, Estela .
IUBMB LIFE, 2008, 60 (08) :483-496