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Dopamine-2 receptor extracellular N-terminus regulates receptor surface availability and is the target of human pathogenic antibodies from children with movement and psychiatric disorders

Overview of attention for article published in Acta Neuropathologica Communications, December 2016
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (81st percentile)
  • Above-average Attention Score compared to outputs of the same age and source (53rd percentile)

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10 tweeters

Citations

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19 Dimensions

Readers on

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33 Mendeley
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Title
Dopamine-2 receptor extracellular N-terminus regulates receptor surface availability and is the target of human pathogenic antibodies from children with movement and psychiatric disorders
Published in
Acta Neuropathologica Communications, December 2016
DOI 10.1186/s40478-016-0397-1
Pubmed ID
Authors

Nese Sinmaz, Fiona Tea, Deepti Pilli, Alicia Zou, Mazen Amatoury, Tina Nguyen, Vera Merheb, Sudarshini Ramanathan, Sandra T. Cooper, Russell C. Dale, Fabienne Brilot

Abstract

Anti-Dopamine-2 receptor (D2R) antibodies have been recently identified in a subgroup of children with autoimmune movement and psychiatric disorders, however the epitope(s) and mechanism of pathogenicity remain unknown. Here we report a major biological role for D2R extracellular N-terminus as a regulator of receptor surface availability, and as a major epitope targeted and impaired in brain autoimmunity. In transfected human cells, purified anti-D2R antibody from patients specifically and significantly reduced human D2R surface levels. Next, human D2R mutants modified in their extracellular domains were subcloned, and we analyzed the region bound by 35 anti-D2R antibody-positive patient sera using quantitative flow cytometry on live transfected cells. We found that N-glycosylation at amino acids N5 and/or N17 was critical for high surface expression in interaction with the last 15 residues of extracellular D2R N-terminus. No anti-D2R antibody-positive patient sera bound to the three extracellular loops, but all patient sera (35/35) targeted the extracellular N-terminus. Overall, patient antibody binding was dependent on two main regions encompassing amino acids 20 to 29, and 23 to 37. Residues 20 to 29 contributed to the majority of binding (77%, 27/35), among which 26% (7/27) sera bound to amino acids R20, P21, and F22, 37% (10/27) patients were dependent on residues at positions 26 and 29, that are different between humans and mice, and 30% (8/27) sera required R20, P21, F22, N23, D26, and A29. Seven patient sera bound to the region 23 to 37 independently of D26 and A29, but most sera exhibited N-glycosylation-independent epitope recognition at N23. Interestingly, no evident segregation of binding pattern according to patient clinical phenotype was observed. D2R N-terminus is a central epitope in autoimmune movement and psychiatric disorders and this knowledge could help the design of novel specific immune therapies tailored to improve patient outcome.

Twitter Demographics

The data shown below were collected from the profiles of 10 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 33 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 33 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 5 15%
Other 4 12%
Student > Master 4 12%
Student > Ph. D. Student 4 12%
Researcher 3 9%
Other 4 12%
Unknown 9 27%
Readers by discipline Count As %
Agricultural and Biological Sciences 6 18%
Medicine and Dentistry 5 15%
Biochemistry, Genetics and Molecular Biology 5 15%
Psychology 3 9%
Neuroscience 2 6%
Other 2 6%
Unknown 10 30%

Attention Score in Context

This research output has an Altmetric Attention Score of 9. 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 08 July 2017.
All research outputs
#2,412,703
of 15,918,909 outputs
Outputs from Acta Neuropathologica Communications
#469
of 941 outputs
Outputs of similar age
#71,745
of 391,159 outputs
Outputs of similar age from Acta Neuropathologica Communications
#52
of 113 outputs
Altmetric has tracked 15,918,909 research outputs across all sources so far. Compared to these this one has done well and is in the 84th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 941 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.3. This one has gotten more attention than average, scoring higher than 50% 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 391,159 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 81% of its contemporaries.
We're also able to compare this research output to 113 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 53% of its contemporaries.