Stathmin 1/2-triggered microtubule loss mediates Golgi fragmentation in mutant SOD1 motor neurons. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Bellouze, Sarah; Baillat, Gilbert; Buttigieg, Dorothée; de la Grange, Pierre; Rabouille, Catherine; Haase, Georg
• Is Part Of: Molecular neurodegeneration. Volume 11:Issue 1(2016)
• Page Start: 1
• Page End: 20
• Publication Date: 2016-12
• Subjects: Neurobiology -- Periodicals; Nervous system -- Diseases -- Periodicals; 616.8
• DOI: 10.1186/s13024-016-0111-6
• Languages: English
• ISSNs: 1750-1326

Abstract

Abstract Background Pathological Golgi fragmentation represents a constant pre-clinical feature of many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) but its molecular mechanisms remain hitherto unclear. Results Here, we show that the severe Golgi fragmentation in transgenic mutant SOD1G85R and SOD1G93A mouse motor neurons is associated with defective polymerization of Golgi-derived microtubules, loss of the COPI coat subunit β-COP, cytoplasmic dispersion of the Golgi tether GM130, strong accumulation of the ER-Golgi v-SNAREs GS15 and GS28 as well as tubular/vesicular Golgi fragmentation. Data mining, transcriptomic and protein analyses demonstrate that both SOD1 mutants cause early presymptomatic and rapidly progressive up-regulation of the microtubule-destabilizing proteins Stathmins 1 and 2. Remarkably, mutant SOD1-triggered Golgi fragmentation and Golgi SNARE accumulation are recapitulated by Stathmin 1/2 overexpression but completely rescued by Stathmin 1/2 knockdown or the microtubule-stabilizing drug Taxol. Conclusions We conclude that Stathmin-triggered microtubule destabilization mediates Golgi fragmentation in mutant SOD1-linked ALS and potentially also in related motor neuron diseases.