Stathmin 1/2-triggered microtubule loss mediates Golgi fragmentation in mutant SOD1 motor neurons

Sarah Bellouze, Gilbert Baillat, Dorothée Buttigieg, Pierre de la Grange, Catherine Rabouille, Georg Haase

Research output: Contribution to journal/periodicalArticleScientificpeer-review

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 SOD1(G85R) and SOD1(G93A) 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.

Original languageEnglish
Pages (from-to)43
JournalMolecular Neurodegeneration
Volume11
Issue number1
DOIs
Publication statusPublished - 2016

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