Endoplasmic Reticulum

ID #1264

I just want to make sure I understand the difference between N-linked glycoslylation and gylcolipid anchors. N-linked glycosylation occurs for any proteins destined for the Golgi, correct? Are the anchors then only added to proteins that will ultimately be embedded in the membrane?

This is basically correct, with just a couple minor (but important) distinctions. First, the vast majority of all proteins that come through the ER do in fact get N-linked glycosylation performed on them, but not absolutely all of them. I didn't really say that explicitly in class, because we generally deal with the rules rather than the exceptions, and in this case the exceptions aren't critical to understand. So long story short, yes, virtually all proteins get glycosylated in the ER.

Second, you're also right that only a subset of the proteins coming through the ER get embedded in the membrane (others, like insulin for example, get dumped outside the cell, and still others end up in a different cellular location). These proteins are called integral membrane proteins. But remember from way back, and a recent reminder in class, that there are 3 different categories of integral membrane proteins. Some are called "membrane associated," meaning they have amino acids that enter the hydrophobic interior of a lipid bilayer but don't cross it. We haven't (and won't) discuss how they get there. The second category was called "transmembrane" proteins, because they cross the membrane. We've now learned how they get inserted into a membrane--in the ER--by combinations of signal sequences and stop transfer sequences. And finally the last (and probably smallest in percentage) category of integral membrane proteins are the lipid-linked proteins. And this is where GPI anchors come into play. Some lipid-linked proteins are covalently attached to a chemically-modified phosphatidyl inositol (PI) molecule in the lumen of the ER, and are now more specifically called GPI-anchored proteins. There are other ways to "lipid-link" a protein, but we don't cover them in this class.

Hope this puts the bigger picture into perspective for everyone!

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