More than 100 years ago, the Golgi apparatus was discovered by Camillo Golgi in Purkinje cells of the cerebellum of the barn owl. It is now known that the Golgi apparatus is presented in all eukaryotic cells where it is a major compartment of the endomembrane system.

Scientists have reported fragmentation of the Golgi apparatus in neurodegenerative disorders including Alzheimer’s disease, Parkinson’s disease, Amyotrophic Lateral Sclerosis and Ataxia. However, it remains unknown that whether disruption of Golgi organization or secretory trafficking can actually cause neurodegeneration or simply reflects a consequence of the neurodegenerative process.

Recently, a research team led by Prof. BAO Shilai at the Institute of Genetics and Developmental Biology of Chinese Academy of Sciences found for the first time that targeted disruption of Golgi organization and secretory trafficking lead to neurodegeneration and ataxia in mice. This study entitled “Loss of the golgin GM130 causes Golgi disruption, Purkinje neuron loss, and ataxia in mice” was published in Proceedings of the National Academy of Sciences of the United States of America as the cover paper.

Researchers generated knockout mice strains lacking the Golgi protein GM130, and found that GM130 is essential for the post-natal growth, survival and motor co-ordination of mice. Deficiency of GM130 in the central nervous system resulted in loss of Purkinje cells in the cerebellum, which explains the ataxia phenotype. Mechanistically, GM130 loss causes fragmentation and defective positioning of the Purkinje cell Golgi, which is accompanied by impaired secretory trafficking to the dendrite, dendritic atrophy, and ultimately cell death.

The findings show that impaired Golgi organization and function cause neurodegeneration in a mammal, and GM130 is required for Golgi organization and positioning as well as protein trafficking in neurons in vivo. Moreover, these results reveal that loss of a widely expressed Golgi protein such as GM130 can lead to a selective neurological phenotype in vivo, a phenomenon not appreciated until now.

This study provides an excellent paradigm for studying the relationship between Golgi dysfunction and neurodegenerative disease, and a better understanding of the pathogenenic mechanisms that underlie neurodegeneration.

This work was supported by grants from the National Science Foundation of China, Chinese Academy of Sciences and Biotechnology and Biological Sciences Research Council.