21 December 2022 at 15:30:00
TGN46 Sorts Secretory Proteins at the Trans-Golgi Network
The trans-Golgi network (TGN) is the central sorting station of the secretory pathway, where cargo proteins are packaged into different transport carriers for export to their respective destination. Despite its fundamental importance in maintaining cellular homeostasis and function, many of the mechanisms of cargo sorting at the TGN still remain elusive. In particular, how secretory cargoes are sorted and specifically packed into CARTS – sphingomyelin-rich and protein kinase D (PKD)-dependent TGN-to-plasma membrane transport carriers ¬– is not known. Here, I will present our results showing that the single-pass type I transmembrane (TM) protein TGN46 (a protein contained in CARTS) plays a key role in the sorting of its clients into nascent carriers. These data reveal that the topological determinants that describe the proper intracellular and intra-Golgi localization of TGN46, as well as its own incorporation in CARTS, are mainly contained in its lumenal domain. Notably, I will present evidence showing that the lumenal domain of TGN46 is both necessary and sufficient for the export of cargo proteins into CARTS and also that this domain mediates the cargo sorting function of TGN46. Altogether, our data suggests an essential role for TGN46 in the sorting of cargo proteins into transport carriers (CARTS) at the TGN.