Week 7 - L3 - Notes on Golgi Apparatus Function and Protein Transport

Understanding the Golgi Apparatus
- Focus on protein sorting to various destinations
- Emphasis on retrieval and secretory pathways

Description of the Golgi Apparatus
- Composed of stacks or sacs of membranes, similar to the endoplasmic reticulum (ER)
- Proteins enter through the cis Golgi and exit via the trans Golgi
Movement of Proteins
- Proteins and vesicles move from the ER to Golgi and then to their final destinations
- Control mechanisms are in place for protein movement and retrieval

Entry and Exit Points
- Cis Golgi: Entry point for proteins from the ER
- Trans Golgi: Exit point for proteins directed to other locations
Key Differences in Membrane-Bound Enzymes
- Distinct enzymes and processing machinery are present in cis and trans Golgi

Purpose of Retrieval Pathway
- To ensure ER resident proteins do not accidentally leave the ER
- Prevents loss of protein function if ER residents are secreted
Mechanism for Soluble ER Residents
  - Soluble ER proteins have a specific KDEL (or KDAL) sequence
  - Recognized by KDEL receptors in the Golgi membrane
  - Triggers vesicle budding utilizing COP I coat proteins
  - Triggered by pH: lower pH in vesicles favors binding, higher pH in the ER triggers release
Mechanism for Membrane-Bound ER Residents
- Membrane-bound proteins have a Kd sequence (variable) but do not require separate receptors
- Directly bind to COP-coated vesicles for retrieval

General Processing Functions
- Golgi modifies oligosaccharides or sugar chains attached to proteins
- Modifications influence final protein function
Specific Processing Examples
  - Phosphorylation of Mannose: Important for targeting proteins to lysosomes
    - Removal of mannose and addition of galactose and other carbohydrates occurs at this stage
    - Significant for proper protein destination and function

Overview of Exit Pathways
- Major pathways include:
- Lysosomal targeting, constitutive secretory pathway, and regulated secretory pathway
Constitutive Secretory Pathway
- Newly synthesized soluble or membrane-bound proteins are secreted as they are synthesized and processed
- Includes plasma membrane proteins and lipids contributing to the membrane structure
Regulated Secretory Pathway
- Specific proteins are stored in vesicles and released under certain signaling conditions (e.g., neurotransmitters or hormones)

Importance of Sidedness
  - The sidedness is maintained throughout vesicular transport
  - Enzymatic processing occurs within the lumen of the Golgi and ER
  - Sugars added during processing ultimately affect the external profile of proteins, important for cell recognition and immune response

Example: Cystic Fibrosis (CF)
- Caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein
- CFTR is a chloride channel essential for ion balance in epithelial cells
Effect of Protein Misfolding
  - Common mutation (deletion 508) leads to misfolding and degradation of CFTR, absence in epithelial membranes
  - Disruption of normal channel trafficking illustrates the importance of regulatory checks in the secretory pathway
  - Consequences: Increased mucus production, inflammation, susceptibility to infections, and reduced lifespan

Key Concepts Recap
- Golgi's role in protein processing, retrieval pathways for ER residents, and the importance of glycosylation
- Protein destinations include plasma membranes, secretory vesicles, and lysosomes
Preview of Next Content
- Continued discussion of cell trafficking and introduction to topics regarding cell death.