Mannose-6-phosphate receptors (MPRs) transport lysosomal hydrolases from the 
trans Golgi network (TGN) to endosomes. Recently, the multi-ligand receptor 
sortilin has also been implicated in this transport, but the transport carriers 
involved herein have not been identified. By quantitative immuno-electron 
microscopy, we localized endogenous sortilin of HepG2 cells predominantly to the 
TGN and endosomes. In the TGN, sortilin colocalized with MPRs in the same 
clathrin-coated vesicles. In endosomes, sortilin and MPRs concentrated in 
sorting nexin 1 (SNX1)-positive buds and vesicles. SNX1 depletion by small 
interfering RNA resulted in decreased pools of sortilin in the TGN and an 
increase in lysosomal degradation. These data indicate that sortilin and MPRs 
recycle to the TGN in SNX1-dependent carriers, which we named endosome-to-TGN 
transport carriers (ETCs). Notably, ETCs emerge from early endosomes (EE), lack 
recycling plasma membrane proteins and by three-dimensional electron tomography 
exhibit unique structural features. Hence, ETCs are distinct from hitherto 
described EE-derived membranes involved in recycling. Our data emphasize an 
important role of EEs in recycling to the TGN and indicate that different, 
specialized exit events occur on the same EE vacuole.