Title |
Endocytosis regulates TDP-43 toxicity and turnover
|
---|---|
Published in |
Nature Communications, December 2017
|
DOI | 10.1038/s41467-017-02017-x |
Pubmed ID | |
Authors |
Guangbo Liu, Alyssa N. Coyne, Fen Pei, Spencer Vaughan, Matthew Chaung, Daniela C. Zarnescu, J. Ross Buchan |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United Kingdom | 1 | 33% |
United States | 1 | 33% |
Unknown | 1 | 33% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 67% |
Scientists | 1 | 33% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 137 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 36 | 26% |
Student > Master | 17 | 12% |
Student > Bachelor | 16 | 12% |
Researcher | 13 | 9% |
Student > Doctoral Student | 10 | 7% |
Other | 12 | 9% |
Unknown | 33 | 24% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 39 | 28% |
Neuroscience | 32 | 23% |
Agricultural and Biological Sciences | 14 | 10% |
Medicine and Dentistry | 5 | 4% |
Pharmacology, Toxicology and Pharmaceutical Science | 4 | 3% |
Other | 6 | 4% |
Unknown | 37 | 27% |