TGNtoendosome

The TGNtoendosome pathway refers to the transport of cargo proteins and lipids from the trans‑Golgi network (TGN) to early endosomes. This route is distinct from the retrograde movement to the Golgi or the exocytic pathway to the plasma membrane. It involves a series of vesicular carriers that are formed at the TGN and fuse with endosomal membranes, thereby delivering membrane proteins and sorting signals for degradation or recycling.

Key molecular players in the TGNtoendosome route include ARF family GTPases such as ARF6, whose activation coordinates the budding of vesicles. The adaptor protein complex AP‑1 and the clathrin coat are critical for selecting cargoes and ensuring proper vesicle morphology. Sorting nexins (SNXs) and retromer complexes also modulate the routing of specific receptors, such as the epidermal growth factor receptor, from the TGN to endosomes. Small GTPases of the Rab family, particularly Rab9 and Rab11, regulate later stages of the transport, influencing vesicle docking and fusion with endosomal membranes.

Physiologically, the TGNtoendosome pathway has implications for nutrient uptake, signal transduction, and the regulation of protein turnover. Defects in this pathway can lead to aberrant degradation of surface receptors, contributing to diseases such as cancer and neurodegeneration. For example, impaired trafficking of the transferrin receptor can disrupt iron homeostasis in cells.

Recent imaging studies using fluorescence microscopy and electron tomography have visualized the intermediates of the TGNtoendosome transport. These observations suggest a high degree of coordination between membrane curvature-inducing proteins and the cytoskeletal network, ensuring efficient cargo delivery. Continued research in this area is likely to uncover additional regulatory mechanisms and potential therapeutic targets for disorders associated with vesicular transport dysfunction.