Targeting to Endosomes & Lysosomes

Targeting Proteins to Endosomes and Lysosomes

Overview

• Endosomes originate as vesicles budding from the TGN (Trans-Golgi Network). They can mature into lysosomes, which serve as the cell's degradative compartments, breaking down proteins, RNAs, and other cellular components.

• Lysosomes contain a variety of enzymes capable of degrading different macromolecules.

Mechanism for Targeting Lysosomal Enzymes

Initial Glycosylation and ER to Golgi Transport

• A protein, destined to be a lysosomal enzyme, is initially synthesized in the ER and undergoes glycosylation.

• It is then transported from the ER to the Golgi apparatus.

• Proper folding is ensured before the protein progresses further.

Modification in the CGN (cis-Golgi Network)

• Upon arrival in the CGN, an enzyme present in the CGN adds a GlcNAc-1-phosphate group to the carbon 6 of mannose residues on the protein.

Modification in the MGN (medial-Golgi Network)

• The protein then moves to the MGN, where another enzyme removes the GlcNAc group, leaving only a phosphate group attached to the carbon 6 of mannose.

• This mannose-6-phosphate (M6P) tag serves as the targeting signal for transport to the lysosome.

Packaging and Transport from the TGN (trans-Golgi Network)

• In the TGN, a receptor specific for mannose-6-phosphate binds to the M6P tag on the lysosomal enzymes.

• These enzymes are then packaged into vesicles. These vesicles will then become endosomes which will then develop into lysosomes.