Figure 11.

Proposed mechanism for human GLP-2 receptor agonist-induced internalization and postendocytotic trafficking. The GLP-2R is localized in lipid raft domains on the cell surface in the basal state. After ligand-induced GLP-2R activation, the receptor undergoes desensitization and rapid internalization into neutral lipid raft-derived endosomes, a process that can be blocked by cholesterol sequestration with filipin or cholesterol depletion with methyl-β-cyclodextrin. The receptor is then rapidly and transiently shuttled to early endosomes and then slowly recycled to the cell surface most likely via the pH-sensitive PNRC. Prevention of endosomal acidification with monensin inhibits the recycling of the GLP-2R from the PNRC after ligand-induced endocytosis. L, receptor ligand, GLP-2.