Disposal of Misfolded Gβ in Cells

Heterotrimeric G protein complex is a key component of the G protein-coupled receptor signaling pathway. Its β subunit possesses seven WD repeats that form a propeller-like structure. It is known that Gβ needs chaperon to assist its correct folding. Moreover, its dimerization with Gγ is also essential for both the maintenance of the conformation and the function. How cells handle misfolded Gβ, however, is unclear. Dr. ZHU Xueliang’s group at the Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, has brought an answer to the question.

 

Dr. WAN Yihan and colleagues found that a protein called Nudel bound directly to misfolded Gβ, including polyubiquitinated Gβ that was a substrate of the proteasome. Through the interaction misfolded Gβ was loaded onto cytoplasmic dynein, a molecular motor that moves along microtubules like cars on roads, and then transported to the microtubule-organizing center (MTOC). Such a transport facilitated both the proteasome-mediated degradation of misfolded Gβ and the aggresome-mediated sequestration when the misfolded protein was in excess. Such processes are probably parts of the machinery that controls the quality of newly synthesized Gβ. In addition, the researchers also provided evidence to suggest that the degradation of misfolded Gβ serve as a way to terminate the Gβγ signaling in cells. The work, entitled “Misfolded Gβ is recruited to cytoplasmic dynein by Nudel for efficient clearance”, was published on-line in Cell Research on March 20^th, 2012.

 

This study was supported by grants from the Ministry of Science and Technology, National Natural Science Foundation of China, Science and Technology Commission of Shanghai Municipality, and Chinese Academy of Sciences.

 

AUTHOR CONTACT:

ZHU Xueliang

Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences

Shanghai, China

Phone: 86-21-54921406; E-mail: xlzhu@sibs.ac.cn

 

A model depicting how mfGβ is processed in cells. mfGβ may be generated after either the translation or the Gβγ signaling. It may either be degraded in the cytoplasm or be recruited to dynein by Nudel, followed by the transport to the MTOC for degradation or for sequestration in the form of aggresomes when in excess.