Super-Resolution Microscopy Reveals Presynaptic Localization of the ALS/FTD Related Protein FUS in Hippocampal Neurons

Frontiers in Cellular Neuroscience
Michael SchoenTobias M Boeckers

Abstract

Fused in Sarcoma (FUS) is a multifunctional RNA-/DNA-binding protein, which is involved in the pathogenesis of the neurodegenerative disorders amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). A common hallmark of these disorders is the abnormal accumulation of mutated FUS protein in the cytoplasm. Under normal conditions FUS is confined to the nuclear compartment, in neurons, however, additional somatodendritic localization can be observed. In this study, we carefully analyzed the subcellular localization of endogenous FUS at synaptic sites of hippocampal neurons which are among the most affected cell types in FTD with FUS pathology. We could confirm a strong nuclear localization of FUS as well as its prominent and widespread neuronal expression throughout the adult and developing rat brain, particularly in the hippocampus, the cerebellum and the outer layers of the cortex. Intriguingly, FUS was also consistently observed at synaptic sites as detected by neuronal subcellular fractionation as well as by immunolabeling. To define a pre- and/or postsynaptic localization of FUS, we employed super-resolution fluorescence localization microscopy. FUS was found to be localized within the axon terminal in close pr...Continue Reading

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Citations

Apr 6, 2017·FEBS Letters·Helena Ederle, Dorothee Dormann
Dec 12, 2017·Frontiers in Cellular Neuroscience·Janosch P Heller, Dmitri A Rusakov
Sep 12, 2019·Frontiers in Synaptic Neuroscience·Sofiia Reshetniak, Silvio O Rizzoli
Jan 14, 2017·Frontiers in Cellular Neuroscience·Julia HigelinTobias M Boeckers
Jun 28, 2019·Frontiers in Cellular Neuroscience·Dhruva DeshpandeJens Michaelis
Apr 10, 2020·Frontiers in Neuroscience·Naoki SuzukiMasashi Aoki
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Mar 5, 2016·Journal of Neurochemistry·Hilary A Bowden, Dorothee Dormann
Feb 6, 2020·Frontiers in Molecular Biosciences·Maximilian Paul Thelen, Min Jeong Kye
May 19, 2018·Frontiers in Molecular Biosciences·Shinsuke Ishigaki, Gen Sobue
Aug 8, 2018·International Journal of Molecular Sciences·Stylianos RavanidisEpaminondas Doxakis
Mar 3, 2020·Frontiers in Molecular Biosciences·Joshua A ImperatoreMihaela Rita Mihailescu
Sep 16, 2020·Neuron·Garam KimAaron D Gitler
May 23, 2021·Nature Communications·Sonu SahadevanMagdalini Polymenidou
Nov 13, 2021·Science Advances·Joha ParkKwanghun Chung

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Methods Mentioned

BETA
light microscopy
super-resolution microscopy
antisense oligonucleotides
Fluorescence
fluorescence microscopy
FCS
mechanical dissociation
super resolution microscopy
electrophoresis
fluorescence imaging

Key Resources (RRID) Mentioned

AB_887697
AB_10618753
AB_2247082
AB_2105208
AB_1849181
AB_1860505
AB_307274
AB_887717
AB_477010
AB_1630258

Software Mentioned

dSTORM
COM
MathWorks
ImageJ
Matlab
Axiovison

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