ArticleJCI insight2017
SorCS2-mediated NR2A trafficking regulates motor deficits in Huntington's disease.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Finding memo: versatile interactions of the VPS10p-Domain receptors in Alzheimer's disease.Molecular neurodegeneration · 2022Pooled it
- Visualization of membrane-stabilized SorCS2Journal of structural biology: X · 2026Article
- Huntingtin and its allies at the cortico-striatal synapse.Cell death & disease · 2026Review
- A Multimodal Single-Cell Epigenomic and 3D Genome Atlas of the Human Basal Ganglia.bioRxiv : the preprint server for biology · 2026Article
- Astrocytes distress triggers brain pathology through induction of δ secretase in a murine model of Alzheimer's disease.Nature communications · 2025Article
- A triple serine motif in the intracellular domain of SorCS2 impacts its cellular signaling.iScience · 2025Article
- SorCS2 Is Important for Astrocytic Function in Neurovascular Signaling.Acta physiologica (Oxford, England) · 2025Article
- Fructose Diet-Associated Molecular Alterations in Hypothalamus of Adolescent Rats: A Proteomic Approach.Nutrients · 2023Article
- Loss of SORCS2 is Associated with Neuronal DNA Double-Strand Breaks.Cellular and molecular neurobiology · 2023Article
- Extracellular vesicles improve GABAergic transmission in Huntington's disease iPSC-derived neurons.Theranostics · 2023Article
- The needs of a synapse-How local organelles serve synaptic proteostasis.The EMBO journal · 2022Review
- Beware of Misdelivery: Multifaceted Role of Retromer Transport in Neurodegenerative Diseases.Frontiers in aging neuroscience · 2022Review
- Single neonatal dexamethasone administration has long-lasting outcome on depressive-like behaviour, Bdnf, Nt-3, p75ngfr and sorting receptors (SorCS1-3) stress reactive expression.Scientific reports · 2021Article
- Altered dopaminergic firing pattern and novelty response underlie ADHD-like behavior of SorCS2-deficient mice.Translational psychiatry · 2021Article
- SorCS1-mediated sorting in dendrites maintains neurexin axonal surface polarization required for synaptic function.PLoS biology · 2019Article
- SorCS2 Controls Functional Expression of Amino Acid Transporter EAAT3 and Protects Neurons from Oxidative Stress and Epilepsy-Induced Pathology.Cell reports · 2019Article
- Reduced Alcohol Seeking and Withdrawal Symptoms in Mice Lacking the BDNF Receptor SorCS2.Frontiers in pharmacology · 2019Article
- Structural insights into SorCS2-Nerve Growth Factor complex formation.Nature communications · 2018Article
- Molecular insights into cortico-striatal miscommunications in Huntington's disease.Current opinion in neurobiology · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Motor dysfunction is a prominent and disabling feature of Huntington's disease (HD), but the molecular mechanisms that dictate its onset and progression are unknown. The N-methyl-D-aspartate receptor 2A (NR2A) subunit regulates motor skill development and synaptic plasticity in medium spiny neurons (MSNs) of the striatum, cells that are most severely impacted by HD. Here, we document reduced NR2A receptor subunits on the dendritic membranes and at the synapses of MSNs in zQ175 mice that model HD. We identify that SorCS2, a vacuolar protein sorting 10 protein-domain (VPS10P-domain) receptor, interacts with VPS35, a core component of retromer, thereby regulating surface trafficking of NR2A in MSNs. In the zQ175 striatum, SorCS2 is markedly decreased in an age- and allele-dependent manner. Notably, SorCS2 selectively interacts with mutant huntingtin (mtHTT), but not WT huntingtin (wtHTT), and is mislocalized to perinuclear clusters in striatal neurons of human HD patients and zQ175 mice. Genetic deficiency of SorCS2 accelerates the onset and exacerbates the motor coordination deficit of zQ175 mice. Together, our results identify SorCS2 as an interacting protein of mtHTT and demonstrate that impaired SorCS2-mediated NR2A subunit trafficking to dendritic surface of MSNs is, to our knowledge, a novel mechanism contributing to motor coordination deficits of HD.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.