Defective axonal transport of endo‐lysosomes and dense core vesicles in a Drosophila model of C9‐ALS/FTD

A GGGGCC (G4C2) repeat expansion in the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Although disruptions in axonal transport are implicated in the pathogenesis of multiple neurodegenerative diseases, the underlying mechanisms causing these defects remain unclear. Here, we performed live imaging of Drosophila motor neurons expressing expanded G4C2 repeats in third‐instar larvae and investigated the axonal transport of multiple organelles in vivo. Expression of expanded G4C2 repeats causes an increase in static axonal lysosomes, while it impairs trafficking of late endosomes (LEs) and dense core vesicles (DCVs). Surprisingly, however, axonal transport of mitochondria is unaffected in motor axons expressing expanded G4C2 repeats. Thus, our data indicate that expanded G4C2 repeat expression differentially impacts axonal transport of vesicular organelles and mitochondria in Drosophila models of C9orf72‐associated ALS/FTD.

• Publication year

  2022

• Venue

  Traffic : the International Journal of Intracellular Transport

• Publication date

  2022-07-31

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1111/tra.12861PMID 35908282
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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