Secretory and Endocytic Pathways Flashcards
What do proteins that are targeted to the ER have?
N-terminal signal sequences.
What are signal sequences recognised by?
The signal recognition particle. A cytosolic ribonucleoprotein complex.
What does the SRP do?
Pauses translation to prevent proteins with signal sequences from folding in the cytosol.
What is Sec61?
Where the ribosome binds to displace SRP. Forms a pore in the ER membrane allowing translocation of the protein.
What is BiP?
Binding immunoglobin protein (ER luminal HSP70 chaperone). Required for translocation to the ER. Assembly of non-glycosylated proteins.
What is glycosylation?
OG chain is added by oligoaccharyltransferase to asparagine residues. Associated with Sec61 translocon.
What is calnexin?
A chaperone which prevents proteins folding and aggregating together.
What does trimming do?
Removes 2 glucose residues, leaving a single one. Allows the correct folding.
What is ERAD?
Helps prevent the accumulation of misfolded proteins in the ER which could otherwise aggregate. Removal of mannose residues acts as a molecular clock, required for the addition of glucose.
What is ATF6?
An ER associated membrane protein. ER stress induces cleavage, releasing the N-terminal into the cytosol.
What foes AFT6(N) do?
A transcription factor that induces expression of proteins involved in ER folding.
What is PERK?
An ER-resident transmembrane kinase. Stress causes PERK to phosphorylate eIF2a, inhibiting mRNA translation.
What is IRE1?
A ER transmembrane protein with endoribonuclease activities. Cleaves XBP1 mRNA which promotes expression of genes regulating lipid biosynthetic enzymes.
Name a combination treatment for cystic fibrosis
Lumcaftor + ivacaftor
name two other genetic diseases associated with the ERAD pathway?
osteogenesis imperfecta and a1-antitrypsin deficiency.
Which virus hijacks the ERAD pathway to escape immune recognition?
HCMV by preventing HMC 1 molecules from reaching the plasma membrane.
What do rab proteins do?
bring together membranes that are to fuse
Which toxins can hijack multiple components of the endocytic and secretory pathways to access the ER and use ERAD machinery to access the cytosol?
Cholera and Ricin
What does sec12 do?
Catalyses the GDP-GTP exchange on Sar1 causing it to bind to the membrane. It can then recruit sec23-24 to the ER membrane and recuit cargo proteins. Sec 13-31 drive budding.
What is ERGIC-53?
A receptor which binds to soluble glycoproteins to incorporate them into COPII vesicles.
What is CLSD?
Cranio-lenticulo-structural dysplasia. Skeletal defects and facial abnormalities caused by mutations in sec23a.
What do many ER resident luminal proteins have?
A KDEL retrieval motif.
What happens to N-linked oligosaccharides in the Golgi?
Modification by removal of 3 mannoses.
what causes I-cell disease?
Mutations in N-acetylglucosamine-1-phosphotransferase. Loss of mannose-6-phosphate modification and secretion of lysosomal hydrolyses
What activates signalling cascades?
EGF binding by EGF receptors.
What causes Familial Hypercholesterolaemia?
Disruption of the LDL receptor resulting in CVD.
