Neurobiology of Disease Progressive Motor Neuronopathy: A Critical Role of the Tubulin Chaperone TBCE in Axonal Tubulin Routing from the Golgi Apparatus
نویسندگان
چکیده
Michael K. E. Schaefer,1,2 Henning Schmalbruch,3 Emmanuelle Buhler,1,2 Catherine Lopez,1,2 Natalia Martin,4 Jean-Louis Guénet,4 and Georg Haase1,2 1Inserm, Unité 29, Equipe Avenir, 13273 Marseille, France, 2Aix Marseille Université, Institut de Neurobiologie de la Méditerranée, 13284 Marseille, France, 3Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark, and 4Institut Pasteur, 75015 Paris, France
منابع مشابه
Progressive motor neuronopathy: a critical role of the tubulin chaperone TBCE in axonal tubulin routing from the Golgi apparatus.
Axonal degeneration represents one of the earliest pathological features in motor neuron diseases. We here studied the underlying molecular mechanisms in progressive motor neuronopathy (pmn) mice mutated in the tubulin-specific chaperone TBCE. We demonstrate that TBCE is a peripheral membrane-associated protein that accumulates at the Golgi apparatus. In pmn mice, TBCE is destabilized and disap...
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Progressive motor neuronopathy (pmn) mutant mice have been widely used as a model for human motoneuron disease. Mice that are homozygous for the pmn gene defect appear healthy at birth but develop progressive motoneuron disease, resulting in severe skeletal muscle weakness and respiratory failure by postnatal week 3. The disease starts at the motor endplates, and then leads to axonal loss and f...
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Golgi fragmentation is an early hallmark of many neurodegenerative diseases but its pathophysiological relevance and molecular mechanisms are unclear. We here demonstrate severe and progressive Golgi fragmentation in motor neurons of progressive motor neuronopathy (pmn) mice due to loss of the Golgi-localized tubulin-binding cofactor E (TBCE). Loss of TBCE in mutant pmn and TBCE-depleted motor ...
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Pathological alterations of the Golgi apparatus, such as its fragmentation represent an early pre-clinical feature of many neurodegenerative diseases and have been widely studied in the motor neuron disease amyotrophic lateral sclerosis (ALS). Yet, the underlying molecular mechanisms have remained cryptic. In principle, Golgi fragmentation may result from defects in three major classes of prote...
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