Details

Autor(en) / Beteiligte

• Milojevic, Tetyana
• Reiterer, Veronika
• Stefan, Eduard
• Korkhov, Vladimir M
• Dorostkar, Mario M
• Ducza, Eszter
• Ogris, Egon
• Boehm, Stefan
• Freissmuth, Michael
• Nanoff, Christian

Titel

The Ubiquitin-Specific Protease Usp4 Regulates the Cell Surface Level of the A2a Receptor

Ist Teil von

• Molecular pharmacology, 2006-04, Vol.69 (4), p.1083-1094

Ort / Verlag

United States: American Society for Pharmacology and Experimental Therapeutics

Erscheinungsjahr

2006

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Many membrane proteins incur a folding problem during biosynthesis; only a fraction thereof is exported from the endoplasmic reticulum (ER), because quality control is stringent. This is also true for G protein-coupled receptors. Here, we identify the deubiquitinating enzyme Usp4 as an interaction partner of the A 2a adenosine receptor, a G s -coupled receptor. Usp4 binds to the carboxyl terminus of the A 2A receptor and allows for its accumulation as deubiquinated protein. This relaxes ER quality control and enhances cell surface expression of functionally active receptor. The effect of Usp4 on the A 2A receptor was specific because 1) it was not seen in C-terminally truncated versions of the receptor; 2) it was not mimicked by Usp14, another member of the ubiquitin-specific protease family; and 3) it was not seen with the metabotropic glutamate receptor-5, another G protein-coupled receptor with a high propensity for intracellular retention. These observations show that deubiquinating enzymes can regulate quality control in the ER.