| First Author | Gao X | Year | 2013 |
| Journal | J Biol Chem | Volume | 288 |
| Issue | 36 | Pages | 25760-8 |
| PubMed ID | 23888055 | Mgi Jnum | J:203537 |
| Mgi Id | MGI:5527216 | Doi | 10.1074/jbc.M113.486258 |
| Citation | Gao X, et al. (2013) Splice isoforms of phosducin-like protein control the expression of heterotrimeric G proteins. J Biol Chem 288(36):25760-8 |
| abstractText | Heterotrimeric G proteins play an essential role in cellular signaling; however, the mechanism regulating their synthesis and assembly remains poorly understood. A line of evidence indicates that the posttranslational processing of G protein beta subunits begins inside the protein-folding chamber of the chaperonin containing t-complex protein 1. This process is facilitated by the ubiquitously expressed phosducin-like protein (PhLP), which is thought to act as a CCT co-factor. Here we demonstrate that alternative splicing of the PhLP gene gives rise to a transcript encoding a truncated, short protein (PhLPs) that is broadly expressed in human tissues but absent in mice. Seeking to elucidate the function of PhLPs, we expressed this protein in the rod photoreceptors of mice and found that this manipulation caused a dramatic translational and posttranslational suppression of rod heterotrimeric G proteins. The investigation of the underlying mechanism revealed that PhLPs disrupts the folding of Gbeta and the assembly of Gbeta and Ggamma subunits, events normally assisted by PhLP, by forming a stable and apparently inactive tertiary complex with CCT preloaded with nascent Gbeta. As a result, the cellular levels of Gbeta and Ggamma, which depends on Gbeta for stability, decline. In addition, PhLPs evokes a profound and rather specific down-regulation of the Galpha transcript, leading to a complete disappearance of the protein. This study provides the first evidence of a generic mechanism, whereby the splicing of the PhLP gene could potentially and efficiently regulate the cellular levels of heterotrimeric G proteins. |
