Mammalian Target of Rapamycin Complex 1 (mTORC1) and 2 (mTORC2) Control the Dendritic Arbor Morphology of Hippocampal Neurons

Urbańska, Małgorzata; Gozdz, Agata; Swiech, Lukasz; Jaworski, Jacek

doi:10.1074/jbc.m112.374405

Cited by 137 publications

(136 citation statements)

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“…32 Consistent with previous descriptions, mTORC1 activity was downregulated when we knocked down Rictor with siRNA. Phosphorylation of mTOR and downstream p70S6K were reduced in Rictor knocked-down cells.…”

Section: Knockdown Of Rictor Has Effects Similar To Mir-15a or Mir-16supporting

confidence: 78%

“…9 Through phosphorylation of Akt, mTORC2 can positively regulate the activity of mTORC1. 9,32 It would be reasonable to speculate that mTORC2 acts as a negative regulator of autophagy. Consistent with this view, inhibition of mTORC2 activity induces autophagy and muscle atrophy through activation of FoxO3, a transcription factor downstream of Akt that induces expression of many autophagy-related genes.…”

Section: Discussionmentioning

confidence: 99%

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MiR-15a and miR-16 induce autophagy and enhance chemosensitivity of Camptothecin

Huang

Qiu

et al. 2015

Cancer Biology & Therapy

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Abbreviations: BAFA1, bafilomycin A1; CPT, Camptothecin; miRNA, microRNA; LC3, microtubule-associated protein 1 light chain 3; mTOR, mechanistic target of rapamycin; Rictor, Rptor independent companion of mTOR complex 2; MUT, mutated; UTR, untranslated region; NC, negative control.It has been reported that persistent or excessive autophagy promotes cancer cell death during chemotherapy, either by enhancing the induction of apoptosis or mediating autophagic cell death. Here, we show that miR-15a and miR-16 are potent inducers of autophagy. Rictor, a component of mTORC2 complex, is directly targeted by miR-15a/16. Overexpression of miR-15a/16 or depletion of endogenous Rictor attenuates the phosphorylation of mTORC1 and p70S6K, inhibits cell proliferation and G1/S cell cycle transition in human cervical carcinoma HeLa cells. Moreover, miR15a/16 dramatically enhances anticancer drug camptothecin (CPT)-induced autophagy and apoptotic cell death in HeLa cells. Collectively, these data demonstrate that miR-15a/16 induced autophagy contribute partly to their inhibition of cell proliferation and enhanced chemotherapeutic efficacy of CPT.

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Section: Knockdown Of Rictor Has Effects Similar To Mir-15a or Mir-16supporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

MiR-15a and miR-16 induce autophagy and enhance chemosensitivity of Camptothecin

Huang

Qiu

et al. 2015

Cancer Biology & Therapy

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“…In our study, rapamycin reduces neural progenitor numbers. Additionally, rapamycin, or the inhibition of the mTORC1 and mTORC2 complexes, have been reported to inhibit dendritic arborization of hippocampal neurons (Urbanska et al 2012). Therefore, chronic rapamycin treatment may have a paradoxical, negative effect on health span.…”

Section: Discussionmentioning

confidence: 99%

Contrasting effects of chronic, systemic treatment with mTOR inhibitors rapamycin and metformin on adult neural progenitors in mice

Kusne

Goldberg

Parker

et al. 2013

AGE

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The chronic and systemic administration of rapamycin extends life span in mammals. Rapamycin is a pharmacological inhibitor of mTOR. Metformin also inhibits mTOR signaling but by activating the upstream kinase AMPK. Here we report the effects of chronic and systemic administration of the two mTOR inhibitors, rapamycin and metformin, on adult neural stem cells of the subventricular region and the dendate gyrus of the mouse hippocampus. While rapamycin decreased the number of neural progenitors, metforminmediated inhibition of mTOR had no such effect. Adult-born neurons are considered important for cognitive and behavioral health, and may contribute to improved health span. Our results demonstrate that distinct approaches of inhibiting mTOR signaling can have significantly different effects on organ function. These results underscore the importance of screening individual mTOR inhibitors on different organs and physiological AGE

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“…DNA Constructs-The following mammalian expression plasmids have been described previously: pSuper vector (30), ␤-actin-GFP (encoding EGFP under control of the ␤-actin promoter), p110CAAX, GW1-HA-RasV12, GW1-HA-RasV12S35, GW1-HA-RasV12S40, pSuper-mTOR7513 (5), ␤-actin-mRFP (encoding mRFP under the control of the ␤-actin promoter) (31), EF␣-␤-gal (32), and pRK5-Myc-S6K1T389E (33). The ␤-actin-TdTomato, encoding TdTomato under control of the ␤-actin promoter, was obtained by subcloning TdTomato coding sequence (34) to modified ␤-actin16pl (35).…”

Section: Methodsmentioning

confidence: 99%

Cyr61, a Matricellular Protein, Is Needed for Dendritic Arborization of Hippocampal Neurons

Malik¹,

Urbańska²,

Gozdz³

et al. 2013

Journal of Biological Chemistry

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Mammalian Target of Rapamycin Complex 1 (mTORC1) and 2 (mTORC2) Control the Dendritic Arbor Morphology of Hippocampal Neurons

Cited by 137 publications

References 50 publications

MiR-15a and miR-16 induce autophagy and enhance chemosensitivity of Camptothecin

MiR-15a and miR-16 induce autophagy and enhance chemosensitivity of Camptothecin

Contrasting effects of chronic, systemic treatment with mTOR inhibitors rapamycin and metformin on adult neural progenitors in mice

Cyr61, a Matricellular Protein, Is Needed for Dendritic Arborization of Hippocampal Neurons

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