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β‐Adrenergic receptor trafficking by exercise in rat adipocytes: roles of G‐protein‐coupled receptor kinase‐2, β‐arrestin‐2, and the ubiquitin‐proteasome pathway
Author(s) -
Ogasawara Junetsu,
Sanpei Minori,
Rahman Nazibur,
Sakurai Tomonobu,
Kizaki Takako,
Hitomi Yoshiaki,
Ohno Hideki,
Izawa Tetsuya
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-4688fje
Subject(s) - arrestin , beta adrenergic receptor kinase , ubiquitin , receptor , proteasome , g protein coupled receptor kinase , lactacystin , chemistry , medicine , endocrinology , agonist , adrenergic receptor , protein kinase a , g protein coupled receptor , microbiology and biotechnology , biology , kinase , biochemistry , gene
The effect of exercise on β‐adrenergic receptor (β‐AR) trafficking was investigated in rat adipocytes. The binding sites of a hydrophilic ligand, [ 3 H]CGP12177, increased immediately (0 h) and at 3 h after exercise (3 h) but decreased at 24 h after exercise (24 h). The data of immunoblotting revealed that the alterations in the binding sites mainly paralleled the alterations in the β 2 ‐AR proteins in membrane fractions. The protein expressions of both G‐protein‐coupled receptor kinase (GRK)‐2 and β‐arrestin‐2 were reduced, with a decline in β 2 ‐AR ubiquitination at 0 h and 3 h. The protein expressions of β 2 ‐AR, GRK‐2, β‐arrestin‐2, the β 2 ‐AR/β‐arrestin‐2 complex, and β 2 ‐AR ubiquitination returned to their respective control levels at 24 h, whereas the β 2 ‐AR mRNA level was reduced. Administration of either lactacystin or propranolol did not alter GRK‐2 and β 2 ‐AR protein expressions after exercise. Thus, the mechanism underlying the increased density of β 2 ‐AR up to at least 3 h may involve alterations in a multistep event involving the coordinate interaction among proteins mediating β 2 ‐AR trafficking, in which both the receptor‐agonist interactions and ubiquitin‐proteasome pathway have a key role. However, the decreased protein expression of β 2 ‐AR at 24 h might be due to some change occurring at the translational levels.