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Quantitative proteomic analysis of Parkin substrates in Drosophila neurons

Overview of attention for article published in Molecular Neurodegeneration, April 2017
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (86th percentile)
  • High Attention Score compared to outputs of the same age and source (88th percentile)

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1 news outlet
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12 tweeters
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1 Facebook page

Citations

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32 Dimensions

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68 Mendeley
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Title
Quantitative proteomic analysis of Parkin substrates in Drosophila neurons
Published in
Molecular Neurodegeneration, April 2017
DOI 10.1186/s13024-017-0170-3
Pubmed ID
Authors

Aitor Martinez, Benoit Lectez, Juanma Ramirez, Oliver Popp, James D. Sutherland, Sylvie Urbé, Gunnar Dittmar, Michael J. Clague, Ugo Mayor

Abstract

Parkin (PARK2) is an E3 ubiquitin ligase that is commonly mutated in Familial Parkinson's Disease (PD). In cell culture models, Parkin is recruited to acutely depolarised mitochondria by PINK1. PINK1 activates Parkin activity leading to ubiquitination of multiple proteins, which in turn promotes clearance of mitochondria by mitophagy. Many substrates have been identified using cell culture models in combination with depolarising drugs or proteasome inhibitors, but not in more physiological settings. Here we utilized the recently introduced BioUb strategy to isolate ubiquitinated proteins in flies. Following Parkin Wild-Type (WT) and Parkin Ligase dead (LD) expression we analysed by mass spectrometry and stringent bioinformatics analysis those proteins differentially ubiquitinated to provide the first survey of steady state Parkin substrates using an in vivo model. We further used an in vivo ubiquitination assay to validate one of those substrates in SH-SY5Y cells. We identified 35 proteins that are more prominently ubiquitinated following Parkin over-expression. These include several mitochondrial proteins and a number of endosomal trafficking regulators such as v-ATPase sub-units, Syx5/STX5, ALiX/PDCD6IP and Vps4. We also identified the retromer component, Vps35, another PD-associated gene that has recently been shown to interact genetically with parkin. Importantly, we validated Parkin-dependent ubiquitination of VPS35 in human neuroblastoma cells. Collectively our results provide new leads to the possible physiological functions of Parkin activity that are not overtly biased by acute mitochondrial depolarisation.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 68 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 68 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 17 25%
Researcher 14 21%
Student > Master 8 12%
Student > Bachelor 4 6%
Lecturer 3 4%
Other 11 16%
Unknown 11 16%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 21 31%
Agricultural and Biological Sciences 12 18%
Neuroscience 9 13%
Medicine and Dentistry 5 7%
Engineering 2 3%
Other 7 10%
Unknown 12 18%

Attention Score in Context

This research output has an Altmetric Attention Score of 14. 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 06 June 2018.
All research outputs
#1,056,655
of 13,046,126 outputs
Outputs from Molecular Neurodegeneration
#67
of 556 outputs
Outputs of similar age
#35,983
of 262,678 outputs
Outputs of similar age from Molecular Neurodegeneration
#2
of 18 outputs
Altmetric has tracked 13,046,126 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 91st percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 556 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.4. This one has done well, scoring higher than 87% of its peers.
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 262,678 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 86% of its contemporaries.
We're also able to compare this research output to 18 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 88% of its contemporaries.