Evidence map›Paper›PMID 27839998›Full record

ArticleNeuron2016

Enzymatic Activity of the Scaffold Protein Rapsyn for Synapse Formation.

Lei Li, Yu Cao, Haitao Wu, Xinchun Ye, Zhihui Zhu, Guanglin Xing, Chengyong Shen, Arnab Barik, Bin Zhang, Xiaoling Xie and 5 more

Open access · bronzeAbstract read
In one paragraph

Article in Neuron, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
4.2field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

51 citing papers in PubMed, 83 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Neddylation E1 Obligatory Subunit Nae1 Is Critical to Neuromuscular Junction Development and Maintenance.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Article
  5. Article
  6. Neddylation steers the fate of cellular receptors.Experimental & molecular medicine · 2024
    Review
  7. Article
  8. Article
  9. The MuSK agonist antibody protects the neuromuscular junction and extends the lifespan in C9orf72-ALS mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
  10. Article
  11. Article
  12. Building, Breaking, and Repairing Neuromuscular Synapses.Cold Spring Harbor perspectives in biology · 2024
    Review
  13. Article
  14. Review
  15. Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 2 institutions in 1 country.

Lei LiDepartment of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Yu CaoDepartment of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Haitao WuDepartment of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Xinchun YeDepartment of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Zhihui ZhuDepartment of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Guanglin XingDepartment of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Chengyong ShenDepartment of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Arnab BarikDepartment of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Bin ZhangDepartment of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Xiaoling XieDepartment of Ophthalmology, University of Rochester, Rochester, NY 14642, USA.
Wenbo ZhiCenter for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Lin GanDepartment of Ophthalmology, University of Rochester, Rochester, NY 14642, USA.
Huabo SuVascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Wen-Cheng XiongDepartment of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA; Department of Neurology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA; Charlie Norwood VA Medical Center, Augusta, GA 30912, USA.
Lin MeiDepartment of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA; Department of Neurology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA; Charlie Norwood VA Medical Center, Augusta, GA 30912, USA. Electronic address: lmei@augusta.edu.
Augusta University · USUniversity of Rochester · US

Funding

Mechanisms of neuromuscular junction formationR01NS082007 · NINDS · CASE WESTERN RESERVE UNIVERSITY · PI XIONG, WEN-CHENG · 2013 to 2022
$5.2M
Neddylation and cardiac protein quality controlR01HL124248 · NHLBI · AUGUSTA UNIVERSITY · PI SU, HUABO · 2014 to 2024
$4.1M
SIGNALING MECHANISMS REGULATING ACHR SYNTHESIS AT NMJR01NS040480 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI MEI, LIN · 2000 to 2013
$3.6M
Characterization of Agrin/LRP4 Antibody-Positive Myasthenia GravisR01NS090083 · NINDS · CASE WESTERN RESERVE UNIVERSITY · PI MEI, LIN · 2015 to 2019
$2.9M
Swedish APP mutation and NMJ decline in Alzheimer's diseaseR01AG051510 · NIA · CASE WESTERN RESERVE UNIVERSITY · PI XIONG, WEN-CHENG, ZIGMOND, RICHARD E · 2015 to 2024
$2.6M
Neuromuscular Junction FormationR01NS056415 · NINDS · AUGUSTA UNIVERSITY · PI MEI, LIN · 2008 to 2011
$1.4M
NHLBI NIH HHS R01 HL124248NIA NIH HHS R01 AG051510NINDS NIH HHS R01 NS040480NINDS NIH HHS R01 NS056415NINDS NIH HHS R01 NS082007NINDS NIH HHS R01 NS090083
6 · The paper itself

Abstract

Neurotransmission is ensured by a high concentration of neurotransmitter receptors at the postsynaptic membrane. This is mediated by scaffold proteins that bridge the receptors with cytoskeleton. One such protein is rapsyn (receptor-associated protein at synapse), which is essential for acetylcholine receptor (AChR) clustering and NMJ (neuromuscular junction) formation. We show that the RING domain of rapsyn contains E3 ligase activity. Mutation of the RING domain that abolishes the enzyme activity inhibits rapsyn- as well as agrin-induced AChR clustering in heterologous and muscle cells. Further biological and genetic studies support a working model where rapsyn, a classic scaffold protein, serves as an E3 ligase to induce AChR clustering and NMJ formation, possibly by regulation of AChR neddylation. This study identifies a previously unappreciated enzymatic function of rapsyn and a role of neddylation in synapse formation, and reveals a potential target of therapeutic intervention for relevant neurological disorders.

Indexed as

AgrinAnimalsCytoskeletonMiceMuscle Fibers, SkeletalMuscle ProteinsNeuromuscular JunctionReceptors, CholinergicSynapsesUbiquitin-Protein LigasesAgrinMuscle Proteinsperipheral membrane protein 43KReceptors, CholinergicUbiquitin-Protein LigasesAChRE3 ligaseneddylationrapsynRING domain

Identifiers

PMID27839998
PMCPMC5366040
OpenAlexW2555790226

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.