Module 7.2 - GPCR 2

Endosome Acidification and Receptor Internalization

• Endosomes along the degradation pathway have progressively lower pH, reaching pH 5, to enhance the function of enzymes like lysosomes.
• Acidification in endosomes occurs to separate receptors from their ligands and discourage protein-protein interactions without denaturing proteins.
• Ectopically expressed sst2A somatostatin receptors are rapidly internalized in living cells and recycle slowly.
• Postendocytic trafficking of sst2A involves desensitization, internalization through clathrin-coated vesicles, transport to endosomes, and eventual return to the cell surface in a slow process taking approximately 60 minutes.
• Internalized sst2A receptors reside in a syntaxin-6positive compartment distinct from the TGN and the recycling endosome.
• The drug Brefeldin A does not disperse internalized somatostatin receptors, putting into question the idea that internalized receptors are stored in the TGN.
• Internalized sst2A receptors reside in vesicles containing syntaxin-6 but not TGN38 or PIST, suggesting a new model of sequestration and regulated recycling.
• Glucose transporter type 4 (GLUT4) in basal conditions has very few on the plasma membrane and mostly sits in storage vesicles inside the cell.
• Insulin triggers rapid transport and fusion of Glut4 storage vesicles to the plasma membrane to bring glucose rapidly.
• GSV-like vesicles (GSVLs) mediate a regulated type of recycling similar to GSVs, and they are recycled in response to hormonal signaling.
• GSV-like carriers (GSVLs) are recycled in response to hormonal signaling and internalize SSTR2 receptors, leading to their return to normal levels after stimulation.
• GSV-like carriers (GSVLs) mediate a similar system to Glut4 storage vesicles, releasing insulin under stress in adipose tissue, and regulate activity of adrenal gland, stimulating cortisol hormone production.

Endosome Acidification and Receptor Internalization

• Endosomes along the degradation pathway have progressively lower pH, reaching pH 5, to enhance the function of enzymes like lysosomes.
• Acidification in endosomes occurs to separate receptors from their ligands and discourage protein-protein interactions without denaturing proteins.
• Ectopically expressed sst2A somatostatin receptors are rapidly internalized in living cells and recycle slowly.
• Postendocytic trafficking of sst2A involves desensitization, internalization through clathrin-coated vesicles, transport to endosomes, and eventual return to the cell surface in a slow process taking approximately 60 minutes.
• Internalized sst2A receptors reside in a syntaxin-6positive compartment distinct from the TGN and the recycling endosome.
• The drug Brefeldin A does not disperse internalized somatostatin receptors, putting into question the idea that internalized receptors are stored in the TGN.
• Internalized sst2A receptors reside in vesicles containing syntaxin-6 but not TGN38 or PIST, suggesting a new model of sequestration and regulated recycling.
• Glucose transporter type 4 (GLUT4) in basal conditions has very few on the plasma membrane and mostly sits in storage vesicles inside the cell.
• Insulin triggers rapid transport and fusion of Glut4 storage vesicles to the plasma membrane to bring glucose rapidly.
• GSV-like vesicles (GSVLs) mediate a regulated type of recycling similar to GSVs, and they are recycled in response to hormonal signaling.
• GSV-like carriers (GSVLs) are recycled in response to hormonal signaling and internalize SSTR2 receptors, leading to their return to normal levels after stimulation.
• GSV-like carriers (GSVLs) mediate a similar system to Glut4 storage vesicles, releasing insulin under stress in adipose tissue, and regulate activity of adrenal gland, stimulating cortisol hormone production.