Association of Golgi Stacks and Recycling Endosomes Ensures Post-Golgi Trafficking

The trans-Golgi network (TGN) has traditionally been considered the primary sorting hub for newly synthesized proteins, whereas recycling endosomes (REs) are recognized as intermediate stations for endocytosed materials before their return to the plasma membrane. However, over the past two decades, functional overlaps between the TGN and RE have become evident, with both playing roles in the exocytic and endocytic pathways. Recent studies have shown that REs can transition between two distinct states: Golgi-associated RE (GA-RE) and free-RE. Detachment and reattachment of REs to Golgi stacks are commonly observed. In plants, it has been established that there are two types of TGNs: Golgi-associated TGN and Golgi-independent TGN. The dynamics of REs in animal cells strongly resemble those in plant TGNs. Together with their molecular similarities, these findings suggest that REs may be equivalent to at least some parts of the TGN. Given that the TGN is now understood to be composed of distinct zones, REs could represent the trans-most zone of the TGN.GA-REs receive newly synthesized glycosylphosphatidylinositol-anchored proteins (GPI-APs) but not vesicular stomatitis virus G protein (VSV-G) from the trans-Golgi cisternae. Upon detachment from the Golgi stacks, free-REs serve as post-Golgi carriers for GPI-APs. Besides cargo sorting, the TGN/RE system may play a key role in regulating the spatial distribution of Golgi stacks within cells. We propose that the dynamic balance between the association and separation of Golgi stacks and TGNs/REs is crucial for determining the cell-wide arrangement of Golgi stacks, along with the organization of microtubules and the lateral-linking activity of Golgi stacks.