Golgi fragmentation precedes neuromuscular denervation and is associated with endosome abnormalities in SOD1-ALS mouse motor neurons

Vera van Dis, Marijn Kuijpers, Elize D Haasdijk, Eva Teuling, Scott A Oakes, Casper C Hoogenraad, Dick Jaarsma

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BACKGROUND: Fragmentation of stacked cisterns of the Golgi apparatus into dispersed smaller elements is a feature associated with degeneration of neurons in amyotrophic lateral sclerosis (ALS) and some other neurodegenerative disorders. However, the role of Golgi fragmentation in motor neuron degeneration is not well understood.

RESULTS: Here we use a SOD1-ALS mouse model (low-copy Gurney G93A-SOD1 mouse) to show that motor neurons with Golgi fragmentation are retrogradely labeled by intramuscularly injected CTB (beta subunit of cholera toxin), indicating that Golgi fragmentation precedes neuromuscular denervation and axon retraction. We further show that Golgi fragmentation may occur in the absence of and precede two other pathological markers, i.e. somatodendritic SOD1 inclusions, and the induction of ATF3 expression. In addition, we show that Golgi fragmentation is associated with an altered dendritic organization of the Golgi apparatus, does not depend on intact apoptotic machinery, and is facilitated in transgenic mice with impaired retrograde dynein-dependent transport (BICD2-N mice). A connection to altered dynein-dependent transport also is suggested by reduced expression of endosomal markers in neurons with Golgi fragmentation, which also occurs in neurons with impaired dynein function.

CONCLUSIONS: Together the data indicate that Golgi fragmentation is a very early event in the pathological cascade in ALS that is associated with altered organization of intracellular trafficking.

Original languageEnglish
Article number38
JournalActa neuropathologica communications
Publication statusPublished - 2014


  • Activating Transcription Factor 3
  • Amyotrophic Lateral Sclerosis
  • Animals
  • Calcitonin Gene-Related Peptide
  • Carrier Proteins
  • Cells, Cultured
  • Cholera Toxin
  • Choline O-Acetyltransferase
  • Disease Models, Animal
  • Endosomes
  • Golgi Apparatus
  • Humans
  • Membrane Proteins
  • Mice
  • Mice, Transgenic
  • Motor Neurons
  • Nerve Tissue Proteins
  • Neuromuscular Diseases
  • Superoxide Dismutase
  • Vesicular Transport Proteins

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