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Genetic ablation of dynactin p150Glued in postnatal neurons causes preferential degeneration of spinal motor neurons in aged mice

Overview of attention for article published in Molecular Neurodegeneration, March 2018
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  • Above-average Attention Score compared to outputs of the same age (55th percentile)

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Title
Genetic ablation of dynactin p150Glued in postnatal neurons causes preferential degeneration of spinal motor neurons in aged mice
Published in
Molecular Neurodegeneration, March 2018
DOI 10.1186/s13024-018-0242-z
Pubmed ID
Authors

Jia Yu, Chen Lai, Hoon Shim, Chengsong Xie, Lixin Sun, Cai-Xia Long, Jinhui Ding, Yan Li, Huaibin Cai

Abstract

Dynactin p150Glued, the largest subunit of the dynactin macromolecular complex, binds to both microtubules and tubulin dimers through the N-terminal cytoskeleton-associated protein and glycine-rich (CAP-Gly) and basic domains, and serves as an anti-catastrophe factor in stabilizing microtubules in neurons. P150Gluedalso initiates dynein-mediated axonal retrograde transport. Multiple missense mutations at the CAP-Gly domain of p150Gluedare associated with motor neuron diseases and other neurodegenerative disorders, further supporting the importance of microtubule domains (MTBDs) in p150Gluedfunctions. However, most functional studies were performed in vitro. Whether p150Gluedis required for neuronal function and survival in vivo is unknown. Using Cre-loxP genetic manipulation, we first generated a line of p150Gluedknock-in mice by inserting two LoxP sites flanking the MTBD-coding exons 2 to 4 of p150Glued-encoding Dctn1 gene (Dctn1LoxP/), and then crossbred the resulting Dctn1LoxP/mice with Thy1-Cre mice to generate the bigenic p150Glued(Dctn1LoxP/LoxP; Thy1-Cre) conditional knockout (cKO) mice for the downstream motor behavioral and neuropathological studies. P150Gluedexpression was completely abolished in Cre-expressing postnatal neurons, including corticospinal motor neurons (CSMNs) and spinal motor neurons (SMNs), while the MTBD-truncated forms remained. P150Gluedablation did not affect the formation of dynein/dynactin complex in neurons. The p150GluedcKO mice did not show any obvious developmental phenotypes, but exhibited impairments in motor coordination and rearing after 12 months of age. Around 20% loss of SMNs was found in the lumbar spinal cord of 18-month-old cKO mice, in company with increased gliosis, neuromuscular junction (NMJ) disintegration and muscle atrophy. By contrast, no obvious degeneration of CSMNs, striatal neurons, midbrain dopaminergic neurons, cerebellar granule cells or Purkinje cells was observed. Abnormal accumulation of acetylated α-tubulin, and autophagosome/lysosome proteins was found in the SMNs of aged cKO mice. Additionally, the total and cell surface levels of glutamate receptors were also substantially elevated in the p150Glued-depleted spinal neurons, in correlation with increased vulnerability to excitotoxicity. Overall, our findings demonstrate that p150Gluedis particularly required to maintain the function and survival of SMNs during aging. P150Gluedmay exert its protective function through regulating the transportation of autophagosomes, lysosomes, and postsynaptic glutamate receptors in neurons.

Twitter Demographics

The data shown below were collected from the profiles of 5 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 27 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 27 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 5 19%
Student > Doctoral Student 3 11%
Researcher 3 11%
Student > Postgraduate 2 7%
Lecturer 2 7%
Other 5 19%
Unknown 7 26%
Readers by discipline Count As %
Medicine and Dentistry 5 19%
Neuroscience 4 15%
Agricultural and Biological Sciences 4 15%
Nursing and Health Professions 3 11%
Business, Management and Accounting 1 4%
Other 2 7%
Unknown 8 30%

Attention Score in Context

This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 03 March 2018.
All research outputs
#7,287,657
of 13,789,144 outputs
Outputs from Molecular Neurodegeneration
#373
of 580 outputs
Outputs of similar age
#119,402
of 272,239 outputs
Outputs of similar age from Molecular Neurodegeneration
#1
of 1 outputs
Altmetric has tracked 13,789,144 research outputs across all sources so far. This one is in the 46th percentile – i.e., 46% of other outputs scored the same or lower than it.
So far Altmetric has tracked 580 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.6. This one is in the 34th percentile – i.e., 34% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 272,239 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 55% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them