Endoplasmic Reticulum

ID #2449

I'm kind of confused with the GPI anchors. The book says that "their orientation within the ER dictates that GPI anchored proteins are exposed on the outside of the cell". It makes sense for it to be on the outside, but the pictures all show the entire protein in the lumen. How is the whole thing flipped around so the N terminus is outside?

Remember, when it comes to the ER and transmembrane proteins: anything that starts out facing the cytoplasm will always face the cytoplasm. Anything that starts out in the lumen will always face the lumen or eventually end up on the outside of the cell. The GPI anchored proteins are no exception. 
After proceeding through the Golgi apparatus, the vesicle containing the GPI anchored protein will fuse with the plasma membrane of the cell, leaving the vesicle's lumen facing the outside of the cell. 
The lumen is analogous to the outside of the cell. When a lipid-linked protein is being transported to the plasma membrane in a secretory vesicle, the GPI anchored-protein will be facing the lumen of the vesicle. Once the vesicle fuses with the plasma membrane, the lipid-linked protein will now be facing the extracellular space outside of the cell. (If a given transmembrane protein is facing the cytoplasm at any stage during secretion, it will always face the cytoplasm even once it reaches the plasma membrane). If you are still having difficulty picturing how this works I would recommend either drawing it out or visiting a TA or Prof. Mehrtens during office hours. 
Lipid-linked proteins are always displayed on the outside of cells, so the GPI anchor will be added to a protein in the lumen of the ER so that it is positioned properly to face the outside of the cell once it is transported to the plasma membrane. A lipid-linked protein will never face the cytoplasm. 

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