1. Nicotinamide Mononucleotide Adenylyltransferase 2 maintains neuronal structural integrity through the maintenance of golgi structure
- Author
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Clayton Mansel, Bhupinder P.S. Vohra, Tana S Pottorf, Alexis Mann, and Shaneann Fross
- Subjects
0301 basic medicine ,Programmed cell death ,Golgi Apparatus ,Apoptosis ,Bcl-xL ,Caspase 6 ,Mice ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,symbols.namesake ,Ganglia, Spinal ,medicine ,Animals ,Nicotinamide-Nucleotide Adenylyltransferase ,RNA, Small Interfering ,Axon ,Fragmentation (cell biology) ,Cells, Cultured ,Caspase ,Neurons ,biology ,Chemistry ,Neurodegeneration ,Cell Biology ,Golgi apparatus ,medicine.disease ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,biology.protein ,symbols - Abstract
Golgi fragmentation and loss of Nicotinamide Mononucleotide Adenylyltransferase 2 (NMNAT2) are the early key features of many neurodegenerative disorders. We investigated the link between NMNAT2 loss, Golgi fragmentation and axon degeneration. Golgi fragmentation in the cultured dorsal root ganglion (DRG) neurons resulted in caspase dependent axon degeneration and neuronal cell death. NMNAT2 depletion in the DRG neurons caused Golgi fragmentation and caspase dependent axon degeneration. NMNAT2 depletion did not cause ATP loss in the axons. These results indicate that NMNAT2 is required for maintenance of Golgi structure. Loss of Golgi structure or Nmnat2 depletion causes caspase dependent neurodegeneration. cytNmnat1 overexpression inhibited the axon degeneration induced by Golgi fragmentation or NMNAT2 depletion. These results also suggest that these degeneration signals converge on a common cytNmnat1 mediated axon protective program and are distinct from the SARM1 mediated caspase independent axon degeneration.
- Published
- 2018