ArticleBiological psychiatry2023
Spinophilin Limits Metabotropic Glutamate Receptor 5 Scaffolding to the Postsynaptic Density and Cell Type Specifically Mediates Excessive Grooming.
Article in Biological psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- The genetics of trichotillomania and excoriation disorder: A systematic review.Comprehensive psychiatry · 2024Pooled it
- Proteomic Characterization of Striatal Neurabin Interactome and Its Sex Specific Impact on Motor Behavior.ACS chemical neuroscience · 2026Article
- Striatal spinophilin enhances dopamine D2 receptor (D2R) interaction with cytosolic proteins to mediate persistent D2R agonist-induced locomotor suppression.The Journal of pharmacology and experimental therapeutics · 2026Article
- Multiplexed smFISH Reveals the Spatial Organization of Neuropil Localized mRNAs Is Linked to Abundance.eNeuro · 2025Article
- Placental Igf1 overexpression sex-specifically impacts mouse placenta structure, altering offspring striatal development and behavior.Experimental neurology · 2025Article
- Proximity interactome mapping furthers a role for spinophilin in protein homeostasis.iScience · 2025Article
- Proteomic Characterization of Striatal Neurabin Interactome and its Sex Specific Impact on Motor Behavior.bioRxiv : the preprint server for biology · 2025Article
- Striatal spinophilin enhances D2R interaction with cytosolic proteins to mediate persistent D2R agonist-induced locomotor suppression.bioRxiv : the preprint server for biology · 2025Article
- The E3 Ubiquitin Ligase PRAJA1: A Key Regulator of Synaptic Dynamics and Memory Processes with Implications for Alzheimer's Disease.International journal of molecular sciences · 2025Article
- Proximity labeling and orthogonal nanobody pulldown (ID-oPD) approaches to map the spinophilin interactome uncover a putative role for spinophilin in protein homeostasis.bioRxiv : the preprint server for biology · 2025Article
- Mechanisms of spinophilin-dependent pancreas dysregulation in obesity.American journal of physiology. Endocrinology and metabolism · 2024Article
- Spinophilin-dependent regulation of GluN2B-containing NMDAR-dependent calcium influx, GluN2B surface expression, and cleaved caspase expression.Synapse (New York, N.Y.) · 2023Article
- Mechanisms of spinophilin-dependent pancreas dysregulation underlying diabesity.bioRxiv : the preprint server for biology · 2023Article
- Characterization of endoplasmic reticulum-associated degradation in the human fungal pathogenPeerJ · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundGrooming dysfunction is a hallmark of the obsessive-compulsive spectrum disorder trichotillomania. Numerous preclinical studies have utilized SAPAP3-deficient mice for understanding the neurobiology of repetitive grooming, suggesting that excessive grooming is caused by increased metabotropic glutamate receptor 5 (mGluR5) activity in striatal direct- and indirect-pathway medium spiny neurons (MSNs). However, the MSN subtype-specific signaling mechanisms that mediate mGluR5-dependent adaptations underlying excessive grooming are not fully understood. Here, we investigated the MSN subtype-specific roles of the striatal signaling hub protein spinophilin in mediating repetitive motor dysfunction associated with mGluR5 function.
methodsQuantitative proteomics and immunoblotting were utilized to identify how spinophilin impacts mGluR5 phosphorylation and protein interaction changes. Plasticity and repetitive motor dysfunction associated with mGluR5 action were measured using our novel conditional spinophilin mouse model in which spinophilin was knocked out from striatal direct-pathway MSNs and/or indirect-pathway MSNs.
resultsLoss of spinophilin only in indirect-pathway MSNs decreased performance of a novel motor repertoire, but loss of spinophilin in either MSN subtype abrogated striatal plasticity associated with mGluR5 function and prevented excessive grooming caused by SAPAP3 knockout mice or treatment with the mGluR5-specific positive allosteric modulator VU0360172 without impacting locomotion-relevant behavior. Biochemically, we determined that the spinophilin-mGluR5 interaction correlates with grooming behavior and that loss of spinophilin shifts mGluR5 interactions from lipid raft-associated proteins toward postsynaptic density proteins implicated in psychiatric disorders.
conclusionsThese results identify spinophilin as a novel striatal signaling hub molecule in MSNs that cell subtype specifically mediates behavioral, functional, and molecular adaptations associated with repetitive motor dysfunction in psychiatric disorders.
Indexed as
Identifiers
What Socratic 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 Socratic graph.