Endocytosis and Lysosomal Pathway

CBIO3400: Lysosome and Endocytosis Notes

Overview of Endocytosis

  • Endocytosis: The process of taking up materials by invagination of the plasma membrane.
    • Types of endocytic processes:
    • Vesicular Endocytosis: Membrane forms vesicles to take up substances.
    • Phagocytosis: The uptake of larger particles/organisms.
    • Autophagy: Degradation of cellular components through lysosomal action.
    • Macropinocytosis: Non-specific uptake of extracellular fluid and large solutes.

Learning Objectives

  • Understand the process of Endocytosis.
  • Learn about the formation and importance of Clathrin-coated vesicles.
  • Investigate the maturation of endosomes and their significance.
  • Study example pathways like the LDL pathway.
  • Reference for further questions: eLC “CBIO3400 Study Questions L20A”.

Comparison: Exocytosis vs Endocytosis

  • Exocytosis: The process of vesicles fusing with the plasma membrane to release content.
  • Endocytosis: Involves the invagination of the membrane to uptake materials.

Key Terms and Concepts

  • Clathrin: Protein that coats vesicles and facilitates their formation.
  • COPI & COPII: Proteins involved in intracellular transport paths.
  • Retromer: Protein complex that recycles membrane proteins.
  • Endosomes: Organelles involved in sorting endocytosed material.
    • Early Endosome: Formed from vesicles derived from the trans-Golgi network and plasma membrane.
    • Late Endosome: Contains acidic hydrolases and can mature into lysosomes.

Endosome Maturation

  • Early Endosomes

    • Formed from vesicles from the trans-Golgi network and plasma membrane.
    • Relevant as a sorting hub for endocytosed materials.

  • Multivesicular Bodies (MVBs)

    • Formed by the invagination of intracellular vesicles.
    • Degrade activated signal receptors that are no longer needed.

  • Late Endosomes

    • Receive required inactive acidic hydrolases from the trans-Golgi network.
    • Maturation to lysosome occurs through the activation of these hydrolases at low pH.
    • pH progression:
    • Early Endosome: 6.0−6.56.0 - 6.5
    • Late Endosome: 5.0−6.05.0 - 6.0
    • Lysosome: 4.5−5.04.5 - 5.0

Function of Recycling Endosomes

  • Recycling Endosome: Specialized compartments that recycle membrane components back to the plasma membrane.
    • Transport intracellular pool of glucose transporters.

Pathways of Endocytosis

  • Involves fluid uptake and specified molecular uptake via:
    • Phagocytosis: Involves uptake of larger particles (e.g., pathogens).
    • Pinocytosis: Involves non-specific uptake of fluids.
    • Receptor-Mediated Endocytosis: Specific uptake mediated by receptor binding.

Receptor-Mediated Phagocytosis/Endocytosis

  • Example: Neutrophil function in immune response.
    • Neutrophils engulf particles through antibody recognition,
    • Induces signaling cascades leading to cytoskeletal rearrangements and pseudopod formation.

Clathrin-Mediated Endocytosis

  • Clathrin: Protein forms a coat on vesicles during endocytosis.
    • Key process in selective uptake of extracellular molecules such as LDL, transferrin, and hormones.
  • Receptors accumulate in coated pits, which invaginate after ligand binding to form clathrin-coated vesicles.

Clathrin Vesicle Formation

  1. Cargo Receptor: Binds to the substance to be internalized.
  2. Adaptin: Binds cargo receptors and recruits clathrin.
  3. Clathrin Triskelion: Form structures that polymerize into a lattice network.
  4. Dynamin: GTPase required for vesicle fission.
  5. Uncoating: Following vesicle formation, clathrin coats are disassembled with help from Hsp70 and Auxilin.

Example: LDL Pathway

  • LDL (Low Density Lipoprotein) carries cholesterol and apolipoprotein B.
  • LDL receptor binds LDL and facilitates the endocytosis process:
    1. LDL receptors formation in coated pits due to sorting signals.
    2. Apolipoprotein B binds receptors at neutral pH and dissociates at lower pH in endosomes.
    3. Pit invagination and dynamin-mediated vesicle release.
    4. Release of LDL in early endosomes and receptor recycling.
    5. Fusion of early endosomes with late endosomes and subsequent degradation in lysosomes.

Conclusory Notes

  • Understanding endocytic pathways is crucial for comprehending how cells intake materials, including nutrients and signaling molecules, and how immune cells respond to foreign entities.
  • Protocols of clathrin-mediated endocytosis and the LDL pathway illustrate the complexity of intracellular transport and processing.