The KDEL receptor must shuttle back and forth between the ER and the Golgi appar

Question

The KDEL receptor must shuttle back and forth between the ER and the Golgi apparatus in order to accomplish its task of ensuring that soluble ER proteins are retained in the ER lumen. In which compartment does the KDEL receptor bind its ligands more tightly? In which compartment does it bind its ligands more weakly? What is thought to be the basis for its different binding affinities in the two compartments? If your were designing the system, in which compartment would you have the highest concentration of KDEL receptor? Would you predict that the KDEL receptor, which is a transmembrane protein, would itself possess an ER retrieval signal?

Explanation / Answer

The KDEL receptor binds its ligands more tightly in the Golgi apparatus, where it captures proteins that have escaped the ER, so that it can return them. The receptor binds its ligands more weakly in the ER, so that those proteins that have been captured in the Golgi apparatus can be released upon their return to the ER. The basis for the different binding affinities is thought to be the slight difference in pH; the lumen of the Golgi apparatus is slightly more acidic than that of the ER, which is neutral. Since the primary job of the KDEL receptor is to capture proteins that have escaped from the ER, it would be reasonable to design the system so that the receptors are found in the highest concentration in the Golgi apparatus. This is, in fact, the way it is in the cell. You would be correct if you predicted that the KDEL receptor does not have a classic ER retrieval signal; after all, the receptor is designed to spend most of its time in the Golgi apparatus, and a classic signal would ensure its efficient return to the ER. It does, however, have a ‘conditional’ retrieval signal; upon binding to an ER protein in the Golgi apparatus, its conformation is altered so that a binding site for COPI subunits is exposed. That signal allows it to be incorporated into COPIcoated vesicles, which are destined to return to the ER.

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