PUBLICATION

Fluorescence Correlation Spectroscopy Reveals Survival Motor Neuron Oligomerization but No Active Transport in Motor Axons of a Zebrafish Model for Spinal Muscular Atrophy

Authors
Koh, A., Sarusie, M.V., Ohmer, J., Fischer, U., Winkler, C., Wohland, T.
ID
ZDB-PUB-210831-7
Date
2021
Source
Frontiers in cell and developmental biology   9: 639904 (Journal)
Registered Authors
Winkler, Christoph, Wohland, Thorsten
Keywords
active transport, fluorescence correlation spectroscopy, motor axons, smn oligomerization, spinal muscular atrophy, survival motion neuron, zebrafish
MeSH Terms
none
PubMed
34458251 Full text @ Front Cell Dev Biol
Abstract
Spinal Muscular Atrophy (SMA) is a progressive neurodegenerative disease affecting lower motor neurons that is caused by a deficiency in ubiquitously expressed Survival Motor Neuron (SMN) protein. Two mutually exclusive hypotheses have been discussed to explain increased motor neuron vulnerability in SMA. Reduced SMN levels have been proposed to lead to defective snRNP assembly and aberrant splicing of transcripts that are essential for motor neuron maintenance. An alternative hypothesis proposes a motor neuron-specific function for SMN in axonal transport of mRNAs and/or RNPs. To address these possibilities, we used a novel in vivo approach with fluorescence correlation spectroscopy (FCS) in transgenic zebrafish embryos to assess the subcellular dynamics of Smn in motor neuron cell bodies and axons. Using fluorescently tagged Smn we show that it exists as two freely diffusing components, a monomeric, and a complex-bound, likely oligomeric, component. This oligomer hypothesis was supported by the disappearance of the complex-bound form for a truncated Smn variant that is deficient in oligomerization and a change in its dynamics under endogenous Smn deficient conditions. Surprisingly, our FCS measurements did not provide any evidence for an active transport of Smn in axons. Instead, our in vivo observations are consistent with previous findings that SMN acts as a chaperone for the assembly of snRNP and mRNP complexes.
Genes / Markers
Figures
Figure Gallery (5 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
ns12Tg/ns12Tgstandard conditionsLong-pec
ns12Tg/ns12Tgstandard conditionsLong-pec
ns12Tg/ns12Tg + MO1-smn1standard conditionsLong-pec
ns12Tg/ns12Tg + MO1-smn1standard conditionsLong-pec
1 - 4 of 4
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ns12TgTransgenic Insertion
    1 - 1 of 1
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    Human Disease / Model
    Human Disease Fish Conditions Evidence
    spinal muscular atrophyns12Tg/ns12Tg + MO1-smn1standard conditionsTAS
    1 - 1 of 1
    Show
    Sequence Targeting Reagents
    Target Reagent Reagent Type
    smn1MO1-smn1MRPHLNO
    1 - 1 of 1
    Show
    Fish
    Fish
    ns12Tg/ns12Tg
    ns12Tg/ns12Tg + MO1-smn1
    1 - 2 of 2
    Show
    Antibodies
    Orthology
    No data available
    Engineered Foreign Genes
    Marker Marker Type Name
    mCherryEFGmCherry
    1 - 1 of 1
    Show
    Mapping
    No data available
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    Citation
    Koh, A., Sarusie, M.V., Ohmer, J., Fischer, U., Winkler, C., Wohland, T. (2021) Fluorescence Correlation Spectroscopy Reveals Survival Motor Neuron Oligomerization but No Active Transport in Motor Axons of a Zebrafish Model for Spinal Muscular Atrophy. Frontiers in cell and developmental biology. 9:639904.