Loss of the golgin GM130 causes Golgi disruption, Purkinje neuron loss, and ataxia in mice

• DOI: 10.1073/pnas.1608576114
• Publication Date: 2016-12-28T01:50:24Z
• Authors: Chunyi Liu; Mei Mei; Qiuling Li; Peristera Roboti; Qianqian Pang; Zhengzhou Ying; Fei Gao; Martin Lowe; Shilai Bao
• Keywords: Male; Neurons; 0303 health sciences; Secretory Pathway; Golgi Apparatus; Membrane Proteins; Neurodegenerative Diseases; Dendrites; Autoantigens; Mice, Inbred C57BL; Mice; Protein Transport; Purkinje Cells; 03 medical and health sciences; Animals; Ataxia; Female

Significance It has been known for many years that the Golgi apparatus, the central organelle of the secretory pathway, is fragmented upon neurodegenerative disease. However, it has remained an open question whether Golgi disruption contributes to neuronal death, as seen in disease, or is simply a consequence of this process. Here, we show that knocking out the Golgi protein GM130 in mice causes Golgi fragmentation and impaired secretory trafficking in Purkinje neurons, resulting in cell death and ataxia. The cell death and ataxia are first observed in postnatal development, but worsen with age. These findings indicate that targeted disruption of the Golgi apparatus can result in neuronal loss in vivo, supporting the view that Golgi dysfunction can contribute to neurodegeneration.