Reference - Detail
| RRC ID | 64571 |
|---|---|
| Author | Hishinuma S, Nozawa H, Akatsu C, Shoji M. |
| Title | C-terminal of human histamine H1 receptors regulates their agonist-induced clathrin-mediated internalization and G-protein signaling. |
| Journal | J Neurochem |
| Abstract |
It has been suggested that the agonist-induced internalization of G-protein-coupled receptors from the cell surface into intracellular compartments regulates cellular responsiveness. We previously reported that Gq/11 -protein-coupled human histamine H1 receptors internalized via clathrin-dependent mechanisms upon stimulation with histamine. However, the molecular determinants of H1 receptors responsible for agonist-induced internalization remain unclear. In this study, we evaluated the roles of the intracellular C-terminal of human histamine H1 receptors tagged with hemagglutinin (HA) at the N-terminal in histamine-induced internalization in Chinese hamster ovary cells. The histamine-induced internalization was evaluated by the receptor binding assay with [3 H]mepyramine and confocal immunofluorescence microscopy with an anti-HA antibody. We found that histamine-induced internalization was inhibited under hypertonic conditions or by pitstop, a clathrin terminal domain inhibitor, but not by filipin or nystatin, disruptors of the caveolar structure and function. The histamine-induced internalization was also inhibited by truncation of a single amino acid, Ser487, located at the end of the intracellular C-terminal of H1 receptors, but not by its mutation to alanine. In contrast, the receptor-G-protein coupling, which was evaluated by histamine-induced accumulation of [3 H]inositol phosphates, was potentiated by truncation of Ser487, but was lost by its mutation to alanine. These results suggest that the intracellular C-terminal of human H1 receptors, which only comprises 17 amino acids (Cys471-Ser487), plays crucial roles in both clathrin-dependent internalization of H1 receptors and G-protein signaling, in which truncation of Ser487 and its mutation to alanine are revealed to result in biased signaling toward activation of G-proteins and clathrin-mediated internalization, respectively. |
| Volume | 139(4) |
| Pages | 552-565 |
| Published | 2016-11-1 |
| DOI | 10.1111/jnc.13834 |
| PMID | 27566099 |
| MeSH | Animals CHO Cells Cell Membrane / drug effects Cell Membrane / metabolism Clathrin / physiology* Cricetinae Cricetulus Dose-Response Relationship, Drug Endocytosis / drug effects Endocytosis / physiology* GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism* Histamine / pharmacology Histamine Agonists / pharmacology* Histamine H1 Antagonists / pharmacology Humans Receptors, Histamine H1 / chemistry Receptors, Histamine H1 / genetics* Receptors, Histamine H1 / physiology* Signal Transduction / drug effects Signal Transduction / physiology* |
| IF | 4.066 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | CHO-K1(RCB0285) |