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

Autor: Georg Haase, Catherine Rabouille, Dorothée Buttigieg, Gilbert Baillat, Pierre de la Grange, Sarah Bellouze
Přispěvatelé: Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), GenoSplice technology, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Hubrecht Institute for Developmental Biology and Stem Cell Research, Baillat, Gilbert
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Immunoblotting
Mutant
SOD1
Clinical Neurology
Golgi Apparatus
Mice
Transgenic
macromolecular substances
Microtubules
Mice
03 medical and health sciences
symbols.namesake
Cellular and Molecular Neuroscience
Superoxide Dismutase-1
0302 clinical medicine
Microscopy
Electron
Transmission
Microtubule
Journal Article
medicine
Animals
Fragmentation (cell biology)
Molecular Biology
Motor Neurons
Microscopy
Confocal
Chemistry
Amyotrophic Lateral Sclerosis
[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
COPI
Golgi apparatus
Motor neuron
Immunohistochemistry
Cell biology
030104 developmental biology
medicine.anatomical_structure
Cytoplasm
symbols
Stathmin
Neurology (clinical)
Neuroscience
030217 neurology & neurosurgery
Research Article
Zdroj: Molecular Neurodegeneration
Molecular Neurodegeneration, BioMed Central, 2016, 11, pp.43. ⟨10.1186/s13024-016-0111-6⟩
Molecular Neurodegeneration, 2016, 11, pp.43. ⟨10.1186/s13024-016-0111-6⟩
Molecular Neurodegeneration, 11(1). BioMed Central
Molecular Neurodegeneration [E], 11(1). BioMed Central
ISSN: 1750-1326
Popis: 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. Electronic supplementary material The online version of this article (doi:10.1186/s13024-016-0111-6) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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