TY  - JOUR
A1  - Markert, Sebastian M.
A1  - Skoruppa, Michael
A1  - Yu, Bin
A1  - Mulcahy, Ben
A1  - Zhen, Mai
A1  - Gao, Shangbang
A1  - Sendtner, Michael
A1  - Stigloher, Christian
T1  - Overexpression of an ALS-associated FUS mutation in C. elegans disrupts NMJ morphology and leads to defective neuromuscular transmission
T2  - Biology Open
N2  - The amyotrophic lateral sclerosis (ALS) neurodegenerative disorder has been associated with multiple genetic lesions, including mutations in the gene for fused in sarcoma (FUS), a nuclear-localized RNA/DNA-binding protein. Neuronal expression of the pathological form of FUS proteins in Caenorhabditis elegans results in mislocalization and aggregation of FUS in the cytoplasm, and leads to impairment of motility. However, the mechanisms by which the mutant FUS disrupts neuronal health and function remain unclear. Here we investigated the impact of ALS-associated FUS on motor neuron health using correlative light and electron microscopy, electron tomography, and electrophysiology. We show that ectopic expression of wild-type or ALS-associated human FUS impairs synaptic vesicle docking at neuromuscular junctions. ALS-associated FUS led to the emergence of a population of large, electron-dense, and filament-filled endosomes. Electrophysiological recording revealed reduced transmission from motor neurons to muscles. Together, these results suggest a pathological effect of ALS-causing FUS at synaptic structure and function organization.
KW  - C. elegans
KW  - fused in sarcoma
KW  - amyotrophic lateral sclerosis
KW  - uper-resolution array tomography
KW  - electron tomography
KW  - neuromuscular junction
Y1  - 2020
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/23066
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-230662
VL  - 9
ER  -