Thyrotropin receptor trafficking relies on the hScrib-ƒÒPIX-GIT1-ARF6 pathway - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue EMBO Journal Année : 2005

Thyrotropin receptor trafficking relies on the hScrib-ƒÒPIX-GIT1-ARF6 pathway

Résumé

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 βPIX–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 βPIX, 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–βPIX–GIT1–ARF6 pathway devoted to TSHR trafficking and function.

Dates et versions

hal-00094094 , version 1 (14-09-2006)

Identifiants

Citer

Olivier Lahuna, Mylène Quellari, Caroline Achard, Sébastien Nola, Géri Méduri, et al.. Thyrotropin receptor trafficking relies on the hScrib-ƒÒPIX-GIT1-ARF6 pathway. EMBO Journal, 2005, 24 (7), pp.1364-1374. ⟨10.1038/sj.emboj.7600616⟩. ⟨hal-00094094⟩
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