VCP/p97 regulates beta(2)AR quality control during receptor biosynthesis

作者：Wargachuk Richard; Glazkova Irina; Audet Nicolas; Petrin Darlaine; Phan Trieu; Hebert Terence E

来源：Cellular Signalling, 2017, 30: 50-58.

DOI：10.1016/j.cellsig.2016.11.015

GPCRs form signalling complexes with other receptors as part of dimers, G proteins and effector partners. A proteomic screen to identify proteins that associate with the beta(2)-adrenergic receptor (beta(2)AR) identified many of components of the Endoplasmic-Reticulum-Associated Degradation (ERAD) quality control system [1], including the valosin-containing protein (VCP/p97). Here, we validated the interaction of VCP with co-expressed FLAG-beta(2)AR, demonstrating, using an inducible expression system, that the interaction of FLAG-beta(2)AR and VCP is not an artifact of overexpression of the beta(2)AR per se. We knocked down VCP and noted that levels of FLAG-beta(2)AR were increased in cells with lower VCP levels. This increase in the level of FLAG-beta(2)AR did not lead to an increase in the level of functional receptor observed at the cell surface. Similarly, inhibition of the proteasome lead to a dramatic increase in the abundance of TAP-beta(2)AR, while cellular responses again remained unchanged. Taken together, our data suggests that a substantial proportion of the beta(2)AR produced is non-functional and VCP plays a key role in the maturation and trafficking of the beta(2)AR as part of the ERAD quality control process.

• 出版日期2017-1
• 单位McGill