ArticleProceedings of the National Academy of Sciences of the United States of America2014
Osteoblast regulation via ligand-activated nuclear trafficking of the oxytocin receptor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 77 citations in OpenAlex.
- Neuroendocrine and neural control of bone mass in health and disease.The Journal of clinical investigation · 2026Review
- Location-biased β-arrestin conformations direct GPCR signaling.Science signaling · 2026Article
- Mechanisms of Location Bias in G Protein-Coupled Receptors.Handbook of experimental pharmacology · 2026Review
- GPCR signaling via cAMP nanodomains.The Biochemical journal · 2025Review
- Unconventional receptor functions and location-biased signaling of the lactate GPCR in the nucleus.Life science alliance · 2025Article
- KPNB1-ATF4 induces BNIP3-dependent mitophagy to drive odontoblastic differentiation in dental pulp stem cells.Cellular & molecular biology letters · 2024Article
- An evolutionary timeline of the oxytocin signaling pathway.Communications biology · 2024Article
- Role of oxytocin in bone.Frontiers in endocrinology · 2024Review
- Pituitary crosstalk with bone, adipose tissue and brain.Nature reviews. Endocrinology · 2023Review
- The Effects of Age on Prostatic Responses to Oxytocin and the Effects of Antagonists.Biomedicines · 2023Article
- Acetate-Mediated Odorant Receptor OR51E2 Activation Results in Calcitonin Secretion in Parafollicular C-Cells: A Novel Diagnostic Target of Human Medullary Thyroid Cancer.Biomedicines · 2023Article
- The mechanism of oxytocin and its receptors in regulating cells in bone metabolism.Frontiers in pharmacology · 2023Review
- GPCRs in Intracellular Compartments: New Targets for Drug Discovery.Biomolecules · 2022Review
- Functional Characterization of Sugar Transporter CRT1 Reveals Differential Roles of Its C-Terminal Region in Sugar Transport and Cellulase Induction in Trichoderma reesei.Microbiology spectrum · 2022Article
- Nuclear localization of histamine receptor 2 in primary human lymphatic endothelial cells.Biology open · 2022Article
- Structure-function relationships of the disease-linked A218T oxytocin receptor variant.Molecular psychiatry · 2022Article
- Downregulation of growth plate genes involved with the onset of femoral head separation in young broilers.Frontiers in physiology · 2022Article
- Oxytocin and Bone: Review and Perspectives.International journal of molecular sciences · 2021Review
- Oxytocin Involvement in Body Composition Unveils the True Identity of Oxytocin.International journal of molecular sciences · 2021Review
- Compartmentalized GPCR Signaling from Intracellular Membranes.The Journal of membrane biology · 2021Review
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
We report that oxytocin (Oxt) receptors (Oxtrs), on stimulation by the ligand Oxt, translocate into the nucleus of osteoblasts, implicating this process in the action of Oxt on osteoblast maturation. Sequential immunocytochemistry of intact cells or isolated nucleoplasts stripped of the outer nuclear membrane showed progressive nuclear localization of the Oxtr; this nuclear translocation was confirmed by monitoring the movement of Oxtr-EGFP as well as by immunogold labeling. Nuclear Oxtr localization was conclusively shown by Western immunoblotting and MS of nuclear lysate proteins. We found that the passage of Oxtrs into the nucleus was facilitated by successive interactions with β-arrestins (Arrbs), the small GTPase Rab5, importin-β (Kpnb1), and transportin-1 (Tnpo1). siRNA-mediated knockdown of Arrb1, Arrb2, or Tnpo1 abrogated Oxt-induced expression of the osteoblast differentiation genes osterix (Sp7), Atf4, bone sialoprotein (Ibsp), and osteocalcin (Bglap) without affecting Erk phosphorylation. Likewise and again, without affecting pErk, inhibiting Arrb recruitment by mutating Ser rich clusters of the nuclear localization signal to Ala abolished nuclear import and Oxtr-induced gene expression. These studies define a previously unidentified mechanism for Oxtr action on bone and open possibilities for direct transcriptional modulation by nuclear G protein-coupled receptors.
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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.