title: mTORC2 controls actin polymerization required for consolidation of long-term memory.
abstract: A major goal of biomedical research is the identification of molecular and cellular mechanisms that underlie memory storage. Here we report a previously unknown signaling pathway that is necessary for the conversion from short- to long-term memory. The mammalian target of rapamycin (mTOR) complex 2 (mTORC2), which contains the regulatory protein Rictor (rapamycin-insensitive companion of mTOR), was discovered only recently and little is known about its function. We found that conditional deletion of Rictor in the postnatal murine forebrain greatly reduced mTORC2 activity and selectively impaired both long-term memory (LTM) and the late phase of hippocampal long-term potentiation (L-LTP). We also found a comparable impairment of LTM in dTORC2-deficient flies, highlighting the evolutionary conservation of this pathway. Actin polymerization was reduced in the hippocampus of mTORC2-deficient mice and its restoration rescued both L-LTP and LTM. Moreover, a compound that promoted mTORC2 activity converted early LTP into late LTP and enhanced LTM. Thus, mTORC2 could be a therapeutic target for the treatment of cognitive dysfunction.
authors: Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA.
authors: Wei
authors: W
authors: Huang
authors: Ping Jun
authors: PJ
authors: Zhu
authors: Shixing
authors: S
authors: Zhang
authors: Hongyi
authors: H
authors: Zhou
authors: Loredana
authors: L
authors: Stoica
authors: Mauricio
authors: M
authors: Galiano
authors: Krešimir
authors: K
authors: Krnjević
authors: Gregg
authors: G
authors: Roman
authors: Mauro
authors: M
authors: Costa-Mattioli
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D004330:Drosophila; D006624:Hippocampus / Q000378:metabolism; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D000076225:Mechanistic Target of Rapamycin Complex 2; D057567:Memory, Long-Term / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors / Q000502:physiology*; D009924:Organ Culture Techniques; D058105:Polymerization; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D000199:Actins; D046912:Multiprotein Complexes; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases