Week 8 -L1 - Membrane Transport and Endocytosis Study Notes

Week Eight Overview - Split between two main topics: membrane transport and apoptosis. - Focus on studying lysosomal and endocytic pathways as part of protein trafficking. - Importance of adding to activity sheets that cover protein trafficking content. - Encouragement for questions via Moodle forums or in-class discussions.

Definition: The process by which proteins and contents are brought into the cell.
Roadmap Structure: Overview of how proteins from the membrane or extracellular environment are internalized and processed. - Unique focus on the green pathway (endocytosis pathway).

Plasma Membrane: Starting point for endocytosis.
Early Endosome: - First compartment receiving vesicles after internalization. - Characterized by a lower pH than the cytoplasm. - Key Functions: Processes incoming vesicles, initiating degradation of proteins/components.

Endosome Maturation: Transition from early to late endosome. - Early endosome moves towards becoming a late endosome via maturation, pH decreases further, and hydrolytic enzyme concentration increases.
Late Endosome: - Further processing of contents received from early endosomes. - Incorporates a recycling mechanism to return specific contents, like receptors, back to the plasma membrane. - Recycling Endosome: Special compartments that facilitate the recycling of proteins back to the membrane.

Recycling: Some proteins are sent back to the plasma membrane for reuse (e.g., receptors that formed vesicle pits).
Digestion and Utilization: Some proteins undergo degradation (e.g., cholesterol facilitated by LDL).
Endolysosome: A transitional compartment between endosomes and lysosomes, where initial digestion occurs.
Lysosome: Final destination for degradation; processes and recycles various macromolecules.

Low-Density Lipoprotein (LDL): Key example used to explain the endocytic path and recycling of cholesterol. - Represents the method cells import cholesterol via receptors.
Process: 1. Cargo Receptor: Specific receptors in the plasma membrane bind LDL. 2. Formation of Clathrin-Coated Pit: Involves clathrin and adapter proteins for invagination. 3. Vesicle Budding: Vesicle containing LDL forms and detaches from the membrane. 4. Fusion with Early Endosome: Vesicle combines with early endosome at low pH, aiding in the release of LDL. 5. Receptor Recycling: LDL receptors are recycled back to the plasma membrane. 6. Transport to Late Endosome: From early to late endosome for further processing. 7. Hydrolytic Enzymes: Assist in breaking down LDL contents, liberating cholesterol for cellular use.

Definition: Condition characterized by high levels of cholesterol in the blood, not utilized by cells.
Mechanism Breakdown: Dysfunction in LDL receptor binding and uptake. - Variants of receptors may be produced that are defective, leading to loss of function.
Consequences: High blood cholesterol, potential for cardiovascular complications such as atherosclerosis.
Feedback Mechanism: Lack of cellular uptake fails to regulate cholesterol synthesis, compounding the problem.

Recycling Mechanism: Vesicles from early endosomes to recycling endosomes and back to the plasma membrane.
Example: Glucose Transporters (GLUT4) as recycling components in response to insulin stimulation. - GLUT4 stores in vesicles when not stimulated and moves to the plasma membrane to facilitate glucose uptake during insulin signaling.

Recap of endocytic pathway with emphasis on how it contributes to protein trafficking and cellular functions.
Next video will provide deeper insights into the lysosomal pathway and its implications.