Nicotinamide Mononucleotide Adenylyltransferase 2 maintains neuronal structural integrity through the maintenance of golgi structure

• Published in: Neurochemistry international Vol. 121; pp. 86 - 97
• Main Authors: Pottorf, Tana, Mann, Alexis, Fross, Shaneann, Mansel, Clayton, Vohra, Bhupinder P.S.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2018
• Subjects: Axon degeneration; Bcl-xl; Caspase 6; Dorsal root ganglion; Golgi apparatus fragmentation; Nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2); Bcl-xl; Nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2); Axon degeneration; Dorsal root ganglion; Caspase 6; Golgi apparatus fragmentation
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2018.09.010

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. •Nmnat2 is required for Golgi structural maintenance.•Depletion of NMNAT2 levels or disruption of Golgi structure results in caspase dependent axon degeneration.•NMNAT2 depletion does not cause ATP loss in the axons.•CytNmnat1 overexpression prevented axon degeneration and neuronal soma death in BFA treated or NMNAT2 depleted neurons.•cytNmnat1-mediated axonal protection is independent of Nmnat2 mediated axonal maintenance pathways.