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 |
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Sprache: | eng |
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Zusammenfassung: | 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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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M112.374405 |