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Molecular determinants of orexin receptor‐arrestin‐ubiquitin complex formation
Author(s) -
Jaeger Werner C,
Seeber Ruth M,
Eidne Karin A,
Pfleger Kevin D G
Publication year - 2014
Publication title -
british journal of pharmacology
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12481
Subject(s) - orexin receptor , orexin , arrestin , ubiquitin , receptor , ubiquitin protein ligases , chemistry , neuroscience , biology , microbiology and biotechnology , endocrinology , ubiquitin ligase , g protein coupled receptor , biochemistry , neuropeptide , gene
The orexin system regulates a multitude of key physiological processes, particularly involving maintenance of metabolic homeostasis. Consequently, there is considerable potential for pharmaceutical development for the treatment of disorders from narcolepsy to metabolic syndrome. It acts through the hormonal activity of two endogenous peptides, orexin A binding to orexin receptors 1 and 2 (OX₁ and OX₂) with similar affinity, and orexin B binding to OX₂ with higher affinity than OX₁ receptors. We have previously revealed data differentiating orexin receptor subtypes with respect to their relative stability in forming orexin receptor-arrestin-ubiquitin complexes measured by BRET. Recycling and cellular signalling distinctions were also observed. Here, we have investigated, using BRET, the molecular determinants involved in providing OX₂ receptors with greater β-arrestin-ubiquitin complex stability.