Targeting Proteins to Endosomes and Lysosomes

Targeting Proteins to Endosomes and Lysosomes

Endosomes and Lysosomes

• Endosomes are vesicles budding off the TGN (trans-Golgi network).
• Endosomes can mature into lysosomes.
• Lysosomes function as the cell's garbage disposal, degrading proteins, RNAs, and other macromolecules.
• Lysosomes contain various enzymes to facilitate the degradation process.

Targeting Lysosomal Enzymes

• Lysosomal enzymes are synthesized in the ER and transported to the Golgi.
• Initial glycosylation and proper folding occur in the ER.

CGN (cis-Golgi network)

• An enzyme in the CGN adds a GlcNAc-1-phosphate group to the carbon 6 of mannose residues on the protein.

MGN (medial-Golgi network)

• Another enzyme in the MGN removes the GlcNAc, leaving only the phosphate group attached to the carbon 6 of mannose.
• Mannose-6-phosphate (M6P) serves as the targeting tag for lysosomes.

TGN (trans-Golgi network)

• In the TGN, a receptor binds to the mannose-6-phosphate tag.
• Proteins with the M6P tag are packaged into vesicles.
• These vesicles become endosomes and eventually lysosomes.