| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Ji, Yaoting Calvano, Cosima D. Colaianni, Graziana Tamma, Roberto Yuen, Tony Colucci, Silvia Nico, Beatrice New, Maria I. Sun, Li Mori, Giorgio Zaidi, Mone Grano, Maria Zambonin, Carlo G. Zallone, Alberta Di Benedetto, Adriana Lu, Ping |
| Description |
Author Affiliation: Di Benedetto A ( Department of Basic Medical Science, Neurosciences and Sensory Organs, University of Bari Aldo Moro Medical School, Bari 70126, Italy); Sun L ( Mount Sinai Bone Program and Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029); Zambonin CG ( Department of Chemistry, University of Bari Aldo Moro, Bari 70126, Italy); Tamma R ( Department of Basic Medical Science, Neurosciences and Sensory Organs, University of Bari Aldo Moro Medical School, Bari 70126, Italy); Nico B ( Department of Basic Medical Science, Neurosciences and Sensory Organs, University of Bari Aldo Moro Medical School, Bari 70126, Italy); Calvano CD ( Department of Chemistry, University of Bari Aldo Moro, Bari 70126, Italy); Colaianni G ( Department of Basic Medical Science, Neurosciences and Sensory Organs, University of Bari Aldo Moro Medical School, Bari 70126, Italy); Ji Y ( Mount Sinai Bone Program and Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029); Mori G ( Department of Clinical and Experimental Medicine, University of Foggia, Foggia 71122, Italy); Grano M ( Department of Basic Medical Science, Neurosciences and Sensory Organs, University of Bari Aldo Moro Medical School, Bari 70126, Italy); Lu P ( Mount Sinai Bone Program and Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029); Colucci S ( Department of Basic Medical Science, Neurosciences and Sensory Organs, University of Bari Aldo Moro Medical School, Bari 70126, Italy); Yuen T ( Mount Sinai Bone Program and Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029); New MI ( Departments of Pediatrics and maria.new@mssm.edu mone.zaidi@mountsinai.org.); Zallone A ( Department of Basic Medical Science, Neurosciences and Sensory Organs, University of Bari Aldo Moro Medical School, Bari 70126, Italy); Zaidi M ( Mount Sinai Bone Program and Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029); |
| 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 ß-arrestins (Arrbs), the small GTPase Rab5, importin-ß (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. |
| ISSN |
00278424 |
| e-ISSN |
10916490 |
| Journal |
Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number |
46 |
| Volume Number |
111 |
| Language |
English |
| Publisher |
National Academy of Sciences |
| Publisher Date |
2014-11-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Active Transport, Cell Nucleus Physiology Nuclear Envelope Metabolism Osteoblasts Osteogenesis Oxytocin Receptors, Oxytocin Beta Karyopherins Amino Acid Sequence Amino Acid Substitution Animals Arrestins Antagonists & Inhibitors Genetics Extracellular Signal-Regulated MAP Kinases Gene Expression Regulation Ligands MAP Kinase Signaling System Membrane Proteins Mice Mice, Knockout Molecular Sequence Data Nuclear Proteins Phosphorylation Point Mutation Protein Conformation Protein Processing, Post-Translational RNA, Small Interfering Pharmacology Chemistry Deficiency Recombinant Fusion Proteins Serine Rab5 GTP-Binding Proteins Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Multidisciplinary |
