Secretory Pathways Flashcards
What is the ER continuous with? What is attached to it?
The outer layer of the nuclear envelope. Ribosomes are attached to ER (the rough ER)
If a sugar is put on a transmembrane protein inside the Golgi lumen; which side must the sugar face once it is fused with the membrane? Why?
That sugar will be on the exterior surface of the cell membrane. This is true because the inside of the golgi is continuous with/has the same topological relationship as the outside of the cell
Major function of the ER
Synthesis of lipids (smooth ER). Control of cholesterol homeostatis. Calcium storage (rapid uptake and release). Synthesis of proteins on membrane bound ribosomes (Along with that there is some folding and early post-translational modifications; post-translational insertion into the membrane; quality control)
What are signal sequences?
Part of the translated protein (either destined for cell membrane or to be excreted AKA cargo proteins) that tells the ribosome that is translating it that it needs to go to the ER. This is how ribosomes become associated with RER membrane. Can be found at beginning of protein or internally. Can be in one single stretch or spread throughout and then all the patches associate with each other during folding
What are the 2 ways that cargo proteins get inserted in the ER membrane?
Cotranslational insertion and post-translational insertion (this is not yet well understood. Signal sequence occurs at very end of the protein). We will not focus on the 2nd way today
What is the SRP?
Signal recognition particle. 5 proteins and 1 RNA. Recognizes the signal sequence and stops translation until it is bound to a SRP receptor in the ER membrane
What is a translocon?
A trimer of proteins that forms a channel. Embedded in the ER membrane and attached to the SRP receptor. As the protein is synthesized it is fed through the channel in the translocon so it enters the ER lumen. Highly conserved
What is the signal peptidase?
Protein embedded in ER membrane. It cleaves the signal sequence off the protein once it is inside the ER lumen. Sometimes the signal sequence goes into lumen and gets degraded; sometimes it stayed in membrane and gets degraded
What is the difference between how a cargo protein vs. a membrane protein is made in the ER?
With a cargo protein the whole protein is translated into the lumen of the ER. With a membrane protein part of it is translated into the lumen; then there is a hydrophobic (transmembrane) portion that is recognized by the translocon. This signals to translocon to stop and the rest of the protein (carboxy-terminal end) is tranlated outside of ER.
What is a type 1 transmembrane protein (1 TMD)?
Means it is a transmembrane protein with 1 transmembrane domain. Amino-terminus is inside lumen; carboxy-terminus is on outside
What is a type II transmembrane protein (1 TMD)?
1 transmembrane domain. But now amino end is outside; carboxyl end is inside
What does a 2 TMD protein look like?
2 transmembrane domains. Both carboxyl and amino end are outside (Note: You can have LOTS of transmembrane domains)
What is protein glycosylation? Where does it occur?
Adding of a sugar to hydrophobic regions of the protein as soon as it enters the inside of the ER lumen.
What is the oligosaccharide linked to before it is attached to the protein?
Dolichol - a carrier lipid in the membrane
What is the sequence needed for glycosylation? To which amino acid is the oligosaccharide attached?
Recognition sequence is Asn-X-Ser/Thr (X is any amino acid except proline). Sugar is added to asparagine (Asn)
