ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2015
Integrin β3 Haploinsufficiency Modulates Serotonin Transport and Antidepressant-Sensitive Behavior in Mice.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Neuronal cell adhesion genes and antidepressant response in three independent samples.The pharmacogenomics journal · 2015Trial
- Itgb3 expression is developmentally regulated in pyramidal neurons of mouse cortex and hippocampus.Neuroscience letters · 2026Article
- Modulation of the Mechanosensory Matrisome by Serotonergic Signaling.Results and problems in cell differentiation · 2026Review
- Machine learning models of plasma proteomic data predict mood in chronic stroke and tie it to aberrant peripheral immune responses.Brain, behavior, and immunity · 2023Review
- Integrin β3 regulates apical dendritic morphology of pyramidal neurons throughout hippocampal CA3.Hippocampus · 2023Article
- CRISPR-mediated activation of autism geneMolecular therapy. Nucleic acids · 2022Article
- Integrin β3 in forebrain Emx1-expressing cells regulates repetitive self-grooming and sociability in mice.BMC neuroscience · 2022Article
- Rare Opportunities for Insights Into Serotonergic Contributions to Brain and Bowel Disorders: Studies of the SERT Ala56 Mouse.Frontiers in cellular neuroscience · 2021Article
- Integrin β3 organizes dendritic complexity of cerebral cortical pyramidal neurons along a tangential gradient.Molecular brain · 2020Article
- CeOCellular and molecular neurobiology · 2019Article
- Integrin αVβ3 Function Influences Citalopram Immobility Behavior in the Tail Suspension Test.Frontiers in neuroscience · 2019Article
- Multifaceted Regulations of the Serotonin Transporter: Impact on Antidepressant Response.Frontiers in neuroscience · 2019Review
- Neuroprotective Effect of CeONeurochemical research · 2018Article
- MicroRNA-327 regulates cardiac hypertrophy and fibrosis induced by pressure overload.International journal of molecular medicine · 2018Article
- Blood plasma/IgG N-glycome biosignatures associated with major depressive disorder symptom severity and the antidepressant response.Scientific reports · 2018Article
- The Gain-of-Function Integrin β3 Pro33 Variant Alters the Serotonin System in the Mouse Brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- MicroRNA-Mediated Regulation ofFrontiers in molecular neuroscience · 2017Article
- Decreased sensitivity to paroxetine-induced inhibition of peripheral blood mononuclear cell growth in depressed and antidepressant treatment-resistant patients.Translational psychiatry · 2016Article
- Platelet studies in autism spectrum disorder patients and first-degree relatives.Molecular autism · 2015Article
- Mice lacking integrin β3 expression exhibit altered response to chronic stress.Neurobiology of stressArticle
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Converging lines of evidence have identified genetic interactions between the serotonin transporter (SERT) gene and ITGB3, which encodes the β3 subunit that forms the αIIbβ3 and αvβ3 integrin receptor complexes. Here we examine the consequences of haploinsufficiency in the mouse integrin β3 subunit gene (Itgb3) on SERT function and selective 5-hydroxytryptamine (5-HT) reuptake inhibitor (SSRI) effectiveness in vivo. Biochemical fractionation studies and immunofluorescent staining of murine brain slices reveal that αvβ3 receptors and SERTs are enriched in presynaptic membranes from several brain regions and that αvβ3 colocalizes with a subpopulation of SERT-containing synapses in raphe nuclei. Notably, we establish that loss of a single allele of Itgb3 in murine neurons is sufficient to decrease 5-HT uptake by SERT in midbrain synaptosomes. Pharmacological assays to elucidate the αvβ3-mediated mechanism of reduced SERT function indicate that decreased integrin β3 subunit expression scales down the population size of active SERT molecules and, as a consequence, lowers the effective dose of SSRIs. These data are consistent with the existence of a subpopulation of SERTs that are tightly modulated by integrin αvβ3 and significantly contribute to global SERT function at 5-HT synapses in the midbrain. Importantly, our screen of a normal human population for single nucleotide polymorphisms in human ITGB3 identified a variant associated with reductions in integrin β3 expression levels that parallel our mouse findings. Thus, polymorphisms in human ITGB3 may contribute to the differential responsiveness of select patients to SSRIs.
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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.