1. The Role of Zinc in Axon Formation via the mTORC1 Pathway.
- Author
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Choi S, Kang D, Kang J, Hong DK, Kang BS, Kho AR, Choi BY, Huh SO, and Suh SW
- Subjects
- Animals, Mammals metabolism, Mechanistic Target of Rapamycin Complex 1 metabolism, Mice, Neurons metabolism, Signal Transduction, Axons metabolism, Zinc metabolism
- Abstract
Zinc is an essential micronutrient required for proper function during neuronal development because it can modulate neuronal function and structure. A fully functional description of zinc in axonal processing in the central nervous system remains elusive. Here, we define the role of intracellular zinc in axon formation and elongation, involving the mammalian target of rapamycin complex 1 (mTORC1). To investigate the involvement of zinc in axon growth, we performed an ex vivo culture of mouse hippocampal neurons and administrated ZnCl
2 as a media supplement. At 2 days in vitro, the administration of zinc induced the formation of multiple and elongated axons in the ex vivo culture system. A similar outcome was witnessed in callosal projection neurons in a developing mouse brain. Treatment with extracellular zinc activated the mTORC1 signaling pathway in mouse hippocampal neuronal cultures. The zinc-dependent enhancement of neuronal processing was inhibited either by the deactivation of mTORC1 with RAPTOR shRNA or by mTOR-insensitive 4EBP1 mutants. Additionally, zinc-dependent mTORC1 activation enhanced the axonal translation of TC10 and Par3 may be responsible for axonal growth. We identified a promising role of zinc in controlling axonogenesis in the developing brain, which, in turn, may indicate a novel structural role of zinc in the cytoskeleton and developing neurons., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)- Published
- 2022
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