Clathrin-Dependent Endocytosis Lecture Notes

Clathrin-Dependent Endocytosis

• Clathrin is a coat protein used at the plasma membrane and in the TGN (trans-Golgi network).

• In the TGN, clathrin concentrates mannose-6-phosphates, which tag proteins for delivery to lysosomes.

• Mannose-6-phosphate is the tag for directing proteins to lysosomes.

Pathway Steps

1. Ligand Binding: A ligand binds to its receptor.

2. Migration to Coated Pit: The receptor-ligand complexes migrate to a coated pit.

3. Coat Protein Recruitment:

   • Clathrin serves as the coat protein.

   • Adapter protein is required to hold clathrin onto the membrane.

4. Invagination: Clathrin and adapter protein trigger the invagination (pinching in) of the vesicle.

5. Pinching Off:

   • Dynamin, a GTPase, is required to pinch off the vesicle from the membrane.

   • Dynamin hydrolyzes GTP to GDP, providing energy for vesicle separation.

   • $GTP \rightarrow GDP + P_i$ (Energy Release)

6. Uncoating:

   • An uncoating protein, which is an ATPase, removes the coat proteins.

   • This process requires energy from ATP.

   • $ATP \rightarrow ADP + P_i$ (Energy Release)

7. Coat Protein Recycling: The removed coat proteins return to the cell membrane to form new vesicles.

8. Vesicle Fate: The uncoated vesicle can:

   • Fuse with other endosomes.

   • Become a lysosome.

   • Undergo transcytosis.

Key Proteins

• Clathrin: Coat protein that initiates vesicle formation.

• Adapter Protein: Holds clathrin onto the membrane.

• Dynamin: A GTPase that uses the energy from GTP hydrolysis to pinch off the vesicle from the membrane.

• Uncoating Protein: An ATPase that removes coat proteins from the vesicle.