| First Author | Koliwer J | Year | 2015 |
| Journal | J Biol Chem | Volume | 290 |
| Issue | 10 | Pages | 6120-9 |
| PubMed ID | 25614626 | Mgi Jnum | J:232679 |
| Mgi Id | MGI:5779787 | Doi | 10.1074/jbc.M114.605725 |
| Citation | Koliwer J, et al. (2015) The golgi-associated PDZ domain protein PIST/GOPC stabilizes the beta1-adrenergic receptor in intracellular compartments after internalization. J Biol Chem 290(10):6120-9 |
| abstractText | Many G-protein-coupled receptors carry C-terminal ligand motifs for PSD-95/discs large/ZO-1 (PDZ) domains; via interaction with PDZ domain-containing scaffold proteins, this allows for integration of receptors into signaling complexes. However, the presence of PDZ domain proteins attached to intracellular membranes suggests that PDZ-type interactions may also contribute to subcellular sorting of receptors. The protein interacting specifically with Tc10 (PIST; also known as GOPC) is a trans-Golgi-associated protein that interacts through its single PDZ domain with a variety of cell surface receptors. Here we show that PIST controls trafficking of the interacting beta1-adrenergic receptor both in the anterograde, biosynthetic pathway and during postendocytic recycling. Overexpression and knockdown experiments show that PIST leads to retention of the receptor in the trans-Golgi network (TGN), to the effect that overexpressed PIST reduces activation of the MAPK pathway by beta1-adrenergic receptor (beta1AR) agonists. Receptors can be released from retention in the TGN by coexpression of the plasma membrane-associated scaffold PSD-95, which allows for transport of receptors to the plasma membrane. Stimulation of beta1 receptors and activation of the cAMP pathway lead to relocation of PIST from the TGN to an endosome-like compartment. Here PIST colocalizes with SNX1 and the internalized beta1AR and protects endocytosed receptors from lysosomal degradation. In agreement, beta1AR levels are decreased in hippocampi of PIST-deficient mice. Our data suggest that PIST contributes to the fine-tuning of beta1AR sorting both during biosynthetic and postendocytic trafficking. |
