Week 7 - L2

Vesicles are membrane-bound compartments that facilitate the transport of materials within a cell.
Their formation and targeting to specific destinations are crucial for cellular function.
This discussion focuses on transport from the endoplasmic reticulum (ER) to various destinations, including the extracellular space, Golgi apparatus, and plasma membrane.

The primary compartments involved in vesicular transport are:
  - Endoplasmic Reticulum (ER): Starting point for vesicle formation.
  - Golgi Apparatus: Further processing and sorting of proteins.
  - Plasma Membrane: Final destination for many proteins.
  - Lysosomes: Destination for endocytosed material (discussed in future sessions).
The arrows in the accompanying image represent pathways taken by vesicles, governed by specific tracking and targeting mechanisms.

Vesicles transport both soluble and membrane-bound proteins.
- Soluble Proteins: Free floating in the lumen of the donor compartment.
- Membrane-Bound Proteins: Requires a membrane context for function; e.g., receptors, channels.
Membrane components maintain their orientation (side-ness) during the transport process. The exterior of the donor membrane remains the same after vesicle fusion.

Importance of Coat Proteins: Facilitates the budding of vesicles from membranes.
- Clathrin: A key protein involved in forming vesicles for endocytosis and other pathways.
- COP Proteins: Include COP1 and COP2; aids vesicles derived from the ER and from the Golgi back to the ER.
Structure and Function of Clathrin:
- Clathrin exhibits a triangular structure that facilitates the formation of vesicle shapes from membranes.
- Electron microscopy reveals that clathrin-coated vesicles resemble nets that bud off from the original membrane.

Cargo Recognition: Specific cargo proteins are captured by cargo receptors on the vesicle membrane.
Adapter Proteins: Serve as links between cargo receptors and the clathrin coat.
- These proteins function similarly to a bridge, facilitating the assembly of clathrin around the vesicle.
Bud Formation: The combination of cargo, cargo receptors, adapter proteins, and clathrin initiates the vesicle structural formation.
Dynamin Protein: Assists in pinching off the vesicle from the donor membrane.
- Dynamin creates a neck structure that constricts and separates the vesicle from its donor source.

After vesicle formation, the coat proteins (including clathrin) are shed, resulting in a "naked" vesicle.
Shed coat proteins are often recycled for future vesicle formation.
The naked vesicle must appropriately target its destination to fuse with the correct membrane.

Cytoskeletal Components: Microtubules act as pathways for vesicle transport within the cell.
Motor Proteins: These proteins bind to vesicles and facilitate movement along microtubules, resembling a walking motion.
Rab Proteins and SNARE Proteins: Crucial for vesicle recognition and docking to target membranes.
- Rab Proteins: A large family of proteins that assist with vesicle identification; specific Rab proteins are paired with distinct target membranes.
- SNARE Proteins: Include V-SNAREs on vesicles and T-SNAREs on target membranes necessary for membrane fusion.

Tethering Process: Rab proteins help in tethering the vesicle to the target membrane.
SNARE Interaction: V-SNAREs and T-SNAREs become entwined, tightening the connection between the vesicle and the target membrane.
Membrane Continuity: As the vesicle docks, its membrane becomes continuous with the target membrane.
- This allows for the release of cargo into the target area.

Various Rab proteins specialize in interactions with different membranes:
- Rab1: Targets the ER and Golgi apparatus.
- Numerous family members exist, each responsible for specific membrane interactions.
Understanding this diversity showcases the specificity of vesicle targeting within the cell.

Vesicular transport is vital for the movement of numerous proteins synthesized in the ER toward their operational destinations in the cell.
Both soluble and membrane-bound proteins are transported via vesicular pathways, and the specifics of their movement hinge on the roles of coat proteins, Rab proteins, and SNARE proteins.
This understanding is crucial for comprehending the broader functional capacities of cells and their internal organization, especially regarding membrane dynamics during transport processes.