Secretory Pathways 1 & 2 Flashcards
- Describe the three mechanisms of protein transport.
Process of moving molecules from site of synthesis to site of function/degradation = membrane trafficking (includes exocytic and endocytic pathways). 3 fundamental mechanisms:
1) Gated transport between cytosol and nucleus (nuclear transport)
2) Transmembrane transport across membrane from cytosol into an organelle through translocators (protein synthesis and mitochondrial import)
3) Vesicular transport in which membrane bound transport intermediates move proteins and lipids from one compartment to another
- List the major functions of the ER.
Major organelles of exocytosis = ER (rough and smooth), Golgi, plasma membrane, and vesicles/tubules that serve as transport intermediates.
Major functions of ER (six total for this bitch )=
- Synthesis of lipids primarily in smooth ER (phospholipids, ceramide, and cholesterol)
- Control of cholesterol homeostasis (cholesterol sensor and synthesis)
- Storage of Ca (for rapid uptake and release)
- Synthesis of proteins on membrane bound ribosomes (RER)
- Co-translational folding of proteins and early post-translational modifications
- Quality control
- Describe co-translational translocation for the synthesis of cargo and transmembrane proteins.
- Common pool of ribosomes (can either be free or translocated to RER) used to synthesize proteins that can stay in cytosol or can be transported to ER.
- ER signal sequence on newly formed polypeptide directs ribosome that’s translating it to the ER because it gets bound by SRP (signal recognition particle) (complex of 6 proteins and 1 RNA molecule).
- SRP’s binding pocket is flexible, so it can bind to a variety of different signal sequences.
- When SRP binds ribosome + nascent chain –> causes a pause in translation until the complex binds the SRP receptor at the ER.
- Then ribosome attaches to translocon (protein channel that allows polypeptide chain to enter ER) –> SRP detaches.
- Signal sequence gets cleaved once the polypeptide chain enters the ER lumen.
- If protein is meant to have a TMD (transmembrane domain), mRNA contains a ‘stop transfer’ signal sequence that causes translocon to release peptide and remainder of protein is synthesized in cytosolic face.
- If N-terminal is in cytosol = Type 1 membrane protein; if C-terminal is in cytosol, = Type II membrane protein.
- Membrane proteins with multiple TMDs have multiple internal stop and start transfer sequences.
- Some membrane proteins have a preformed carbohydrate complex added to an asparagine in the ER lumen = N-linked glycosylation (generally on an Asn-X-Ser/Thr part of the chain, where X can be any AA except for Pro).
- This helps to keep proteins from aggregating when hydrophobic domains are exposed, and also because glucose residues act as tags to monitor unfolded proteins.
- Sometimes sugars are removed in ER and then complex glycosylation happen in the Golgi.
- List the major functions of the Golgi.
-Golgi separated into cis, medial and trans Golgi, + the trans Golgi network. pH gradient across Golgi because different enzymes in each section that perform different functions and only work at specific pH. gets more acidic from cis to tgn, this acording to SCOTT POWERS, international man of mystery, is because the enzymes that help with final protein localization require and acidic environment.
- Most of glycosylation of lipids and proteins occurs in Golgi.
- Secretion can be constitutive (secreted right away) and regulated (secreted only when the proper signal is received).
anyways the golgi is still a piece of shit and has four functions:
1) Synthesis of complex sphingolipids from ceramide backbone
2) Additional post-translational modifications of proteins/lipids
3) Proteolytic processing
4) Sorting of proteins and lipids for post-Golgi compartments
- Name three well-studied vesicle coats and describe how these coats function in vesicular transport.
- Movement of cargo and membrane proteins occurs by budding of vesicles, fusion of some of these vesicles into tubules, and fusion of these vesicle/tubules with next compartment.
- This requires the formation of coated vesicles and adapter proteins that recognize the cargo, the coat, and the membrane proteins/lipids destined to move.
- Coat helps with physical deformation of planar membrane. Vesicles can move forward from ER to Golgi, and backwards from Golgi to ER for retrieval. Can also go from Golgi to plasma membrane or other compartments (like lysosome).
- COPII moves vesicles from ER to Golgi;
- COPI from Golgi to ER,
- and clathrin from Golgi to plasma membrane.
woah woah woah guess who fucked up..this lecturer. so he taught us about cholesterol and never taught us how statins work. but dont worry im sure we wont need to know it as doctors. but just in case..
-Statins they block HMG coa reductase, in other words they block the rate limiting step in cholesterol synthesis
-they work so good at preventing cholesterol build up in blood vessels because when you block the synthetic pathway, the body is trying to get more cholesterol so it up-regulates all the enzymes that are actually being blocked
-and also up-regulating the LDL receptor which will get all the LDL cholesterol particles out of the blood –>thus lowering it.
great explanation caldwell.
hey made a point that apparently lysosomes have a huge boner for mannose-6-phosphate… so yeah.
Targeting of soluble enzymes to lysosomes:
Mannose 6-phosphate is a sorting signal for lysosomal proteins. It binds to a receptor that is targeted to vesicles that fuse with the late endosome. In the late endosome pH is low and the receptor and M6P tagged protein dissociate. The endosome delivers the protein to the lysosome and the receptor is recycled.
