Module 7: Focal Sequences and Protein Trafficking - Detailed Notes

Focal Sequences and Protein Trafficking

ER Lumen and Cytosol

• Proteins popped out of the ER lumen pass through the membrane.

• Signal sequences target and feed proteins through the membrane.

Membrane Orientation

• First stretch in membrane.

• Second loop in the cytosol.

• Signal peptidase clips the protein, which becomes packaged into a vesicle and sent to the Golgi apparatus, then to the plasma membrane.

Plasma Membrane Configuration

• Cytosolic face remains facing the cytosol.

• Extracellular world faces the sinusoidal space.

• Modifications like glycosylation occur in the ER lumen or Golgi, so sugars are on the cell's outside surface.

• Lipid bilayer leaflets maintain their orientation: cytosolic leaflet remains cytosolic.

• Flipases can flip leaflets, but generally, the cytosolic leaflet remains cytosolic when it becomes part of the plasma membrane.

• Soluble proteins deposited in the lumen are secreted.

• Proteins not engaging with the signal recognition particle remain cytosolic.

Protein Trafficking

• Membrane proteins journey from the endoplasmic reticulum to the plasma membrane.

• Proteins disperse throughout the ER membrane network and move to exit sites.

• Transport vesicles cluster and move towards the Golgi apparatus near the cell's center.

• Movement is mediated by dynein on microtubules.

• Vesicles then move from the Golgi, potentially containing transmembrane proteins that diffuse laterally within the plasma membrane upon fusion, or secreted proteins transiently visible.

• Depolarizing microtubules halts directed movement, causing diffusion.

• Vesicle coating aids membrane pinching and removal.