title: Loss of the golgin GM130 causes Golgi disruption, Purkinje neuron loss, and ataxia in mice.
abstract: The Golgi apparatus lies at the heart of the secretory pathway where it is required for secretory trafficking and cargo modification. Disruption of Golgi architecture and function has been widely observed in neurodegenerative disease, but whether Golgi dysfunction is causal with regard to the neurodegenerative process, or is simply a manifestation of neuronal death, remains unclear. Here we report that targeted loss of the golgin GM130 leads to a profound neurological phenotype in mice. Global KO of mouse GM130 results in developmental delay, severe ataxia, and postnatal death. We further show that selective deletion of GM130 in neurons causes fragmentation and defective positioning of the Golgi apparatus, impaired secretory trafficking, and dendritic atrophy in Purkinje cells. These cellular defects manifest as reduced cerebellar size and Purkinje cell number, leading to ataxia. Purkinje cell loss and ataxia first appear during postnatal development but progressively worsen with age. Our data therefore indicate that targeted disruption of the mammalian Golgi apparatus and secretory traffic results in neuronal degeneration in vivo, supporting the view that Golgi dysfunction can play a causative role in neurodegeneration.
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.|School of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Chunyi
authors.initials: C
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Mei
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Qiuling
authors.initials: Q
authors.lastname: Li
authors.affiliation: Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, United Kingdom.
authors.forename: Peristera
authors.identifier: 0000-0002-3360-9088
authors.initials: P
authors.lastname: Roboti
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.|School of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Pang
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.|School of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Zhengzhou
authors.initials: Z
authors.lastname: Ying
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.affiliation: Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, United Kingdom; slbao@genetics.ac.cn martin.lowe@manchester.ac.uk.
authors.forename: Martin
authors.initials: M
authors.lastname: Lowe
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; slbao@genetics.ac.cn martin.lowe@manchester.ac.uk.|School of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Shilai
authors.initials: S
authors.lastname: Bao
mesh_terms: D000818:Animals; D001259:Ataxia / Q000378:metabolism*; D001324:Autoantigens / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism; D005260:Female; D006056:Golgi Apparatus / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D019636:Neurodegenerative Diseases / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D011689:Purkinje Cells / Q000378:metabolism*; D055571:Secretory Pathway / Q000502:physiology
chemical_list: D001324:Autoantigens; C097741:Golgin subfamily A member 2; D008565:Membrane Proteins
keywords: GM130; Golgi apparatus; Purkinje cell; ataxia; polarized secretion