Notes on Vesicular Transport Mechanism and Related Processes

Vesicular Transport Mechanism

  • Overview of Vesicular Transport:

    • Proteins enter the Endoplasmic Reticulum (ER) and can either stay in the ER, move to the Golgi apparatus, or be transported elsewhere via vesicular transport.

    • This process involves two main directions:

    • Anterograde (Red): Movement towards the plasma membrane.

    • Retrograde (Blue): Movement back towards the ER.

  • Key Cellular Components:

    • Nucleus, Cytosol, Plastids, Mitochondria, Peroxisomes, Endoplasmic Reticulum, Golgi, Lysosome

Exocytosis and Endocytosis

  • Exocytosis:

    • Process where vesicles fuse with the plasma membrane to release their contents outside the cell.

  • Endocytosis:

    • Formation of vesicles from the plasma membrane to bring material into the cell.

Vesicle Coat Proteins

  • Vesicles are coated with proteins essential for their formation and cargo selection.

    • COPII:

    • Involved in anterograde transport from the ER to the Golgi.

    • COPI:

    • Facilitates retrograde transport back to the ER.

    • Clathrin:

    • Involved in vesicle formation at the trans-Golgi network and plasma membrane.

Golgi Apparatus Compartments

  • Cis Golgi Network:

    • Closest to the ER, where vesicles from the ER fuse.

  • Medial and Trans Golgi:

    • Sites for sorting and packaging of proteins.

Mechanism of Vesicle Formation

  • Initiation involves the G-protein SAR1 being activated to SAR1-GTP in the cytosol, which inserts into the ER membrane, causing membrane curvature.

  • Cargo Selection:

    • Transmembrane cargo proteins have exit signals allowing for interaction with Sec24, part of the COPII coat complex, facilitating cargo incorporation.

Role of Coat Proteins in Vesicle Formation

  • BAR-Domain Proteins:

    • Help induce curvature during vesicle formation.

  • SNARE Insertion:

    • Involves V-SNAREs (on vesicles) and T-SNAREs (on target membranes) which interact and ultimately lead to membrane fusion.

Mechanism of SNARE Insertion

  • V-SNAREs and T-SNAREs wrap around each other, pulling membranes together for fusion, leading to hemifusion before total fusion occurs.

GTP Hydrolysis and Uncoating

  • Uncoating:

    • GTP hydrolysis induces uncoating of the cop II vesicle, allowing for fusion with the target membrane.

    • Auxilin: A chaperone that assists in uncoating by interacting with clathrin-coated vesicles.

Dissociation of SNARE Pairs

  • Post-fusion, V-SNARE and T-SNARE form a trans-SNARE complex.

  • NSF:

    • Uses ATP hydrolysis to untangle SNARE proteins for recycling back to the original membrane.

Homotypic Membrane Fusion

  • Homotypic fusion occurs when identical vesicles, such as those in the ER, fuse to facilitate transport to the Cis-Golgi network.

Rabs and Protein Retrieval

  • Rab Proteins:

    • Important for the specificity of vesicle targeting and fusion processes.