Mannose 6-phosphate receptors (MPRs) bind to their cargo (acid hydrolases) in the trans-Golgi network (TGN), and are packaged into transport carriers that deliver the receptor with its bound ligand to early endosomes (EE).
The low pH within the endosomes facilitates the dissociation of the acid hydrolases from the MPRs.
Dynamic fusion/fission between the late endosomal and lysosomal compartments results in selective delivery of the hydrolases to the lysosome (L) (the ’kiss-and-run’ theory77).
TIP47/Rab9 prevent the MPRs from reaching the lysosomes, in which they would otherwise be degraded.
The return pathway from the early endosomal compartment to the Golgi is probably mediated by PACS-1-assisted packaging into AP1-containing clathrin-coated vesicles (CCVs), whereas that from the late endosomal (LE) compartments is mediated by TIP47 and Rab9.
Some of the MPRs go to the cell surface either from early or late endosomes through the recycling endosome (RE), or from proximal TGN cisternae as a consequence of mis-sorting.
The cell-surface receptors are internalized in AP-2 CCVs and delivered back to the endosomes.
See also
- - mannose-6-phosphate tags
References
Ghosh P, Dahms NM, Kornfeld S. Mannose 6-phosphate receptors: new twists in the tale. Nat Rev Mol Cell Biol 2003 Mar;4(3):202-12