The principle pathway for transport of lysosomal hydrolases from the trans Golgi

Question

The principle pathway for transport of lysosomal hydrolases from the trans Golgi (normally pH 6.6) to the late endosomes (normally pH 6) and for recycling of mannose- 6-phosphate (M6P) receptors back to the Golgi depends on the pH difference between those two compartments. From what you know about M6P receptor binding and recycling and the pathways for delivery of material to lysosomes, describe the consequences of changing the pH in those two compartments.

a. What do you suppose would happen to M6P receptor binding and recycling if the pH in late endosomes were raised to pH 6.6?

b. What do you suppose would happen to M6P receptor binding and recycling if the pH in the trans Golgi network were lowered to pH 6?

Explanation / Answer

Lysosomes are membrane-enclosed compartments filled with hydrolytic enzymes that are used for the controlled intracellular digestion of macromolecules. They contain about 40 types of hydrolytic enzymes, including proteases, nucleases, glycosidases, lipases, phospholipases, phosphatases, and sulfatases. All are acid hydrolases. For optimal activity they require an acidenvironment, and the lysosome provides this by maintaining a pH of about 5.0 in its interior. In this way, the contents of thecytosol are doubly protected against attack by the cell's own digestive system. The membrane of the lysosome normally keeps the digestive enzymes out of the cytosol, but even if they should leak out, they can do little damage at the cytosolic pH of about 7.2.

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