Requirement of TORC1 for late-phase long-term potentiation in the hippocampus.
Late-phase long-term potentiation (L-LTP) and long-term memory depend on the transcription of mRNA of CRE-driven genes and synthesis of proteins. However, how synaptic signals propagate to the nucleus is unclear. Here we report that the CREB coactivator TORC1 (transducer of regulated CREB activity 1) undergoes neuronal activity-induced translocation from the cytoplasm to the nucleus, a process required for CRE-dependent gene expression and L-LTP. Overexpressing a dominant-negative form of TORC1 or down-regulating TORC1 expression prevented activity-dependent transcription of CREB target genes in cultured hippocampal neurons, while overexpressing a wild-type form of TORC1 facilitated basal and activity-induced transcription of CREB target genes. Furthermore, overexpressing the dominant-negative form of TORC1 suppressed the maintenance of L-LTP without affecting early-phase LTP, while overexpressing the wild-type form of TORC1 facilitated the induction of L-LTP in hippocampal slices. Our results indicate that TORC1 is essential for CRE-driven gene expression and maintenance of long-term synaptic potentiation.
Zhou
Yang
Y
Institute of Neuroscience and Key Laboratory of Neurobiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; Graduate School of the Chinese Academy of Sciences, Shanghai, China.
Wu
Hao
H
Li
Shuai
S
Chen
Qian
Q
Cheng
Xue-Wen
XW
Zheng
Jing
J
Takemori
Hiroshi
H
Xiong
Zhi-Qi
ZQ
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000502:physiology; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D015536:Down-Regulation; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D009474:Neurons / Q000502:physiology; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection
C519510:Crtc1 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers; D011994:Recombinant Proteins; D014157:Transcription Factors