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Cited by 97Amyotrophic Lateral Sclerosis ResearchCellular transport and secretionAlzheimer's disease research and treatments

Endocytosis regulates TDP-43 toxicity and turnover

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Liu, Guangbo, Coyne, Alyssa N., Pei, Fen, Vaughan, Spencer, Chaung, Matthew, Zarnescu, Daniela C., Buchan, J. Ross·2017·Nature Communications
DOI 10.1038/s41467-017-02017-xPMC PMC5727062
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Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron degenerative disease. ALS-affected motor neurons exhibit aberrant localization of a nuclear RNA binding protein, TDP-43, into cytoplasmic aggregates, which contributes to pathology via unclear mechanisms. Here, we demonstrate that TDP-43 turnover and toxicity depend in part upon the endocytosis pathway. TDP-43 inhibits endocytosis, and co-localizes strongly with endocytic proteins, including in ALS patient tissue. Impairing endocytosis increases TDP-43 toxicity, aggregation, and protein levels, whereas enhancing endocytosis reverses these phenotypes. Locomotor dysfunction in a TDP-43 ALS fly model is also exacerbated and suppressed by impairment and enhancement of endocytic function, respectively. Thus, endocytosis dysfunction may be an underlying cause of ALS pathology.

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  • Dynamics of endocytosis modulate TDP-43 expression in a TDP-43 amyotrophic lateral sclerosis fly model.

    “In addition, dynamics of endocytosis modulate TDP-43 expression in a TDP-43 ALS fly model [175].”

    From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [175]

    The Results section, “Endocytosis affects TDP-43-induced ALS phenotypes in flies” (page unavailable), shows that altering endocytic proteins changes locomotor dysfunction and neurodegeneration in a TDP-43 fly model. It does not show that endocytosis modulates TDP-43 expression levels in those flies; the reported fly outcomes are TDP-43-induced phenotypes. (LLM, conf=0.85)

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Cited by

Sorted by citations

Authors
Liu, G., Coyne, A. N., Pei, F., Vaughan, S., Chaung, M., Zarnescu, D. C., & Buchan, J. R.
Affiliations
University of Arizona (US)
Corresponding author
Buchan, J. Ross
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2017-12-12
Volume
8
Issue
1
Pages
2092-2092
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-017-02017-x
PMC
PMC5727062
OpenAlex
W2775661933
Cited by
97
References
8
Citations by year
2026: 4 · 2025: 15 · 2024: 11 · 2023: 9 · 2022: 10 · 2021: 18 · 2020: 14 · 2019: 7 · 2018: 9
FWCI
5.72
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UA Campus Repository (The University of Arizona) (acceptedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • ALS Association
  • University of Arizona
  • National Institutes of Health (RO1 NS091299, NS091299)
  • National Institute of General Medical Sciences (R01GM114564)
  • National Institute of Neurological Disorders and Stroke (R01NS091299)
Topics
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
TDP-43, amyotrophic lateral sclerosis, endocytosis, protein turnover, protein aggregation, motor neuron degeneration, RNA-binding proteins, endocytic proteins, locomotor dysfunction, Drosophila model
MeSH terms
Amyotrophic Lateral Sclerosis, Animals, Cell Nucleus, Disease Models, Animal, DNA-Binding Proteins, Drosophila, Endocytosis, Frontal Lobe, Humans, Locomotion, Motor Neurons, RNA-Binding Proteins, HEK293 Cells, Protein Aggregation, Pathological

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