ER to Golgi

Protein Sorting and Trafficking

Introduction

  • After a protein is folded, the next step is to transport it to its correct destination within the cell.

  • The cell employs various mechanisms to ensure proteins reach their intended locations, such as the Golgi apparatus for further processing.

Targeting Signals

  • Amino Acid Sequences:

    • Short sequences of amino acids at the beginning of a protein act as tags.

    • These tags signal where the protein needs to be transported within the cell.

    • Specific amino acid sequences indicate specific destinations.

  • Oligosaccharide Chains:

    • The specific carbohydrate composition (oligosaccharide chain) attached to a protein can determine its destination.

  • Hydrophobic Domains:

    • A span of hydrophobic amino acids indicates that the protein needs to be inserted into a membrane.

    • The length of the hydrophobic span determines which membrane the protein should be inserted into.

Lipid Tagging

  • Phosphate Groups:

    • Lipids can be tagged with phosphate groups to direct them to specific locations.

    • Example: Inositol Kinase

      • Inositol kinase adds phosphate groups to inositols.

      • Inhibiting inositol kinase disrupts trafficking to lysosomes.

      • This indicates that phosphate modification is crucial for lysosomal targeting.

ER Retention and Retrieval

  • Retention in the ER:

    • Proteins that function within the ER can be retained by forming complexes with other structures in the ER.

    • This prevents them from leaving the ER prematurely.

  • Retrieval from the Golgi:

    • Proteins that need to return to the ER from the Golgi have a specific tag: Arginine-any amino acid-Arginine (Arg-X-Arg)

    • This tag triggers packaging in the Trans-Golgi Network (TGN) for transport back to the ER.

Golgi Localization

  • Integral Membrane Proteins:

    • Proteins that function in the Golgi are integral membrane proteins (embedded in the Golgi membrane).

  • Hydrophobic Domain Length:

    • The length of the hydrophobic domain determines which cisterna within the Golgi stack a protein resides in.

    • The thickness of the Golgi membranes varies across the stack:

      • Cis-Golgi Network (CGN): Narrowest membrane

      • Medial-Golgi Network (MGN): Medium-sized membrane

      • Trans-Golgi Network (TGN): Thickest membrane

  • Quality Control:

    • If a protein moves to the TGN but belongs in the MGN, it will be returned to the MGN based on membrane thickness compatibility.

Membrane Thickness and Lipid Modification

  • Dynamic Lipid Composition:

    • The number of carbons in the fatty acid chains of lipids can be adjusted as they move through the Golgi.

    • This ensures the correct membrane thickness for different regions.

  • Context-Specific Thickness:

    • The membrane thickness is not fixed after the ER; it can be modified as needed in different compartments of the endomembrane system.