Cited by 310Memory and Neural MechanismsNeuroscience and Neuropharmacology ResearchPI3K/AKT/mTOR signaling in cancer

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mTORC2 controls actin polymerization required for consolidation of long-term memory

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Huang, Wei, Zhu, Ping Jun, Zhang, Shixing, Zhou, Hongyi, Stoica, Loredana, Galiano, Mauricio, Krnjević, Krešimir, Roman, Gregg, Costa-Mattioli, Mauro·2013·Nature Neuroscience

DOI 10.1038/nn.3351PMC PMC3615448

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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.

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Additional file 5 of mTOR hypoactivity leads to trophectoderm cell failure by enhancing lysosomal activation and disrupting the cytoskeleton in preimplantation embryo
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Additional file 2 of mTOR hypoactivity leads to trophectoderm cell failure by enhancing lysosomal activation and disrupting the cytoskeleton in preimplantation embryo
Ma, C., Li, Q., Yang, Y., Ge, L., Cai, J., Wang, J., Zhu, M., Xiong, Y., Zhang, W., Xie, J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.24709098
Additional file 4 of mTOR hypoactivity leads to trophectoderm cell failure by enhancing lysosomal activation and disrupting the cytoskeleton in preimplantation embryo
Ma, C., Li, Q., Yang, Y., Ge, L., Cai, J., Wang, J., Zhu, M., Xiong, Y., Zhang, W., Xie, J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26647425
Additional file 3 of mTOR hypoactivity leads to trophectoderm cell failure by enhancing lysosomal activation and disrupting the cytoskeleton in preimplantation embryo
Ma, C., Li, Q., Yang, Y., Ge, L., Cai, J., Wang, J., Zhu, M., Xiong, Y., Zhang, W., Xie, J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26647422
Additional file 1 of mTOR hypoactivity leads to trophectoderm cell failure by enhancing lysosomal activation and disrupting the cytoskeleton in preimplantation embryo
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Mitoxyperilysis: A Milestone Discovery in the Field of Cell Death
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Authors: Huang, W., Zhu, P. J., Zhang, S., Zhou, H., Stoica, L., Galiano, M., Krnjević, K., Roman, G., & Costa-Mattioli, M.
Affiliations: Baylor College of Medicine (US)
University of Houston (US)
McGill University (CA)
ORCID: Huang, Wei
Zhu, Ping Jun
Zhang, Shixing
Galiano, Mauricio
Roman, Gregg
Venue: Nature Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 2013-03-03
Volume: 16
Issue: 4
Pages: 441-448
ISSN: 1097-6256 (ISSN-L)
1546-1726
DOI: 10.1038/nn.3351
PMC: PMC3615448
OpenAlex: W1972346280
Cited by: 307
References: 71
Citations by year: 2026: 10 · 2025: 17 · 2024: 22 · 2023: 16 · 2022: 26 · 2021: 21 · 2020: 19 · 2019: 23 · 2018: 27 · 2017: 28 · 2016: 26 · 2015: 29 · 2014: 23 · 2013: 18
FWCI: 17.55
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
Locations: Nature Neuroscience (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Conicet (submittedVersion, cc-by-nc-sa)
Funders: Vanderbilt University
National Institutes of Health (076708, 096816)
National Institute of Mental Health (MH091305, 096816, R01MH096816, MH 096816)
National Institute of Neurological Disorders and Stroke (NS 076708, R01NS076708)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Keywords: mTORC2, Rictor, actin polymerization, long-term memory consolidation, synaptic plasticity, hippocampal long-term potentiation, actin dynamics, conditional knockout mice, Drosophila
MeSH terms: Mechanistic Target of Rapamycin Complex 2, Actins, Animals, Drosophila, Hippocampus, Male, Mice, Inbred C57BL, Mice, Transgenic, Organ Culture Techniques, Long-Term Potentiation, Mice, Knockout, Multiprotein Complexes, Mice, Memory, Long-Term, Polymerization, TOR Serine-Threonine Kinases

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mTORC2 controls actin polymerization required for consolidation of long-term memory

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