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

Dendrites are the main site of information input into neurons. Their development is a multistep process controlled by mammalian target of rapamycin (mTOR) among other proteins. mTOR is a serine/threonine protein kinase that forms two functionally distinct complexes in mammalian cells: mTORC1 and mTO...

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Veröffentlicht in:The Journal of biological chemistry 2012-08, Vol.287 (36), p.30240-30256
Hauptverfasser: Urbanska, Malgorzata, Gozdz, Agata, Swiech, Lukasz J., Jaworski, Jacek
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container_end_page 30256
container_issue 36
container_start_page 30240
container_title The Journal of biological chemistry
container_volume 287
creator Urbanska, Malgorzata
Gozdz, Agata
Swiech, Lukasz J.
Jaworski, Jacek
description Dendrites are the main site of information input into neurons. Their development is a multistep process controlled by mammalian target of rapamycin (mTOR) among other proteins. mTOR is a serine/threonine protein kinase that forms two functionally distinct complexes in mammalian cells: mTORC1 and mTORC2. However, the one that contributes to mammalian neuron development remains unknown. This work used short hairpin RNA against Raptor and Rictor, unique components of mTORC1 and mTORC2, respectively, to dissect mTORC involvement in this process. We provide evidence that both mTOR complexes are crucial for the proper dendritic arbor morphology of hippocampal neurons. These two complexes are required for dendritic development both under basal conditions and upon the induction of mTOR-dependent dendritic growth. We also identified Akt as a downstream effector of mTORC2 needed for proper dendritic arbor morphology, the action of which required mTORC1 and p70S6K1. Background: Neuronal dendrite development is controlled by protein kinases. Results: Knockdown of Raptor or Rictor, components of mammalian target of rapamycin complex (mTORC1 and -2, respectively) inhibits dendritic growth. Conclusion: Both mTORC1 and mTORC2 are needed for dendritic growth, with Akt-mTORC1 acting downstream of mTORC2. Significance: Revealing the mechanism of dendritic growth and mTORC1 and mTORC2 function contributes to the understanding of neuronal plasticity.
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Results: Knockdown of Raptor or Rictor, components of mammalian target of rapamycin complex (mTORC1 and -2, respectively) inhibits dendritic growth. Conclusion: Both mTORC1 and mTORC2 are needed for dendritic growth, with Akt-mTORC1 acting downstream of mTORC2. Significance: Revealing the mechanism of dendritic growth and mTORC1 and mTORC2 function contributes to the understanding of neuronal plasticity.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>22810227</pmid><doi>10.1074/jbc.M112.374405</doi><tpages>17</tpages><oa>free_for_read</oa></addata></record>
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subjects Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Akt PKB
Animals
Carrier Proteins - genetics
Carrier Proteins - metabolism
Dendrite
Dendrites - genetics
Dendrites - metabolism
Dendritic Arbor
HEK293 Cells
Hippocampus - cytology
Hippocampus - metabolism
Humans
Intracellular Signaling Peptides and Proteins - genetics
Intracellular Signaling Peptides and Proteins - metabolism
Mechanistic Target of Rapamycin Complex 1
mTOR
mTOR Complex (mTORC)
Multiprotein Complexes
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Neurobiology
Neurodevelopment
Phosphoproteins - genetics
Phosphoproteins - metabolism
Proteins - genetics
Proteins - metabolism
Proto-Oncogene Proteins c-akt - genetics
Proto-Oncogene Proteins c-akt - metabolism
Rapamycin-Insensitive Companion of mTOR Protein
Raptor
Rats
Regulatory-Associated Protein of mTOR
Ribosomal Protein S6 Kinases, 70-kDa - genetics
Ribosomal Protein S6 Kinases, 70-kDa - metabolism
Rictor
shRNA
TOR Serine-Threonine Kinases
Transcription Factors - genetics
Transcription Factors - metabolism
title Mammalian Target of Rapamycin Complex 1 (mTORC1) and 2 (mTORC2) Control the Dendritic Arbor Morphology of Hippocampal Neurons
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