Thyrotropin receptor trafficking relies on the hScrib-betaPIX-GIT1-ARF6 pathway |
| |
| Authors: | Lahuna Olivier Quellari Mylène Achard Caroline Nola Sébastien Méduri Géri Navarro Christel Vitale Nicolas Borg Jean-Paul Misrahi Micheline |
| |
| Affiliation: | INSERM E120, Récepteurs, Signalisations et Physiopathologie Thyro?dienne et de la Reproduction, Le Kremlin Bicêtre, France. olivier.lahuna@kb.inserm.fr |
| |
| Abstract: | G protein-coupled receptors are regulated by ligand stimulation, endocytosis, degradation of recycling to the cell surface. Little information is available on the molecular mechanisms underlying G protein-coupled receptors recycling. We have investigated recycling of the G protein-coupled thyroid stimulating hormone receptor (TSHR) and found that it relies on hScrib, a membrane-associated PDZ protein. hScrib directly binds to TSHR, inhibits basal receptor endocytosis and promotes recycling, and thus TSHR signalling, at the cell membrane. We previously demonstrated that hScrib is associated with a betaPIX-GIT1 complex comprised of a guanine nucleotide exchange factor and a GTPase-activating protein for ADP ribosylation factors that is involved in vesicle trafficking. We used dominant-negative constructs and small interfering RNA to show that TSHR recycling is regulated by the interaction between hScrib and betaPIX, and by the activity of GIT1. In addition, ARF6, a major target for GIT1, is activated during TSH stimulation of HEK293 and FRTL-5 thyroid cells, and plays a key role in TSHR recycling. Thus, we have uncovered an hScrib-betaPIX-GIT1-ARF6 pathway devoted to TSHR trafficking and function. |
| |
| Keywords: | |
| 本文献已被 PubMed 等数据库收录！ |
|
