The Secretory Pathway Flashcards
what is constitutive exocytosis?
continuous secretion
give an example of regulated secretion?
e.g. just had a meal and get an elevation of blood glucose and gets insulin secretion
what happens in the ER?
- post translational modiciations
- specific proteolytic cleavage
- glycosylation
- disulphide bond formation
- folding and assembly of multiple subunit proteins
what is glycosylation?
covalent addition and processing of oligosaccharides (carbohydrates)
what is involved in the folding and assembly of multiple subunit proteins?
- requires chaperones
- disulphide bond in a protein will be extracellular or secreted protein
- happens in the lumen of the ER
what is correct folding?
- entry is in unfolded form when it enters the ER
- in the ER proteins generally reach their corect confirmation in minutes
- mediated by chaperones
what are chaperones?
- undergo cycles of binding and release of polypeptide substrate
- domains move powered by ATP hydrolysis
- binding and release helps substrate polypeptide adopt correct confirmation
what is disulphide bond formation?
- part of the correct folding process
- the lumen is oxidising whereas the cytoplasm is reducing
- get sulphur cross-linked (uses protein duslphide isomerase (PDI))
what does prolyl isomerase do?
proline isomerisation
what configuration do most peptide bonds need to be in?
trans configuration - more favourable
what configuration is proline?
can be in the cis or in the trans state
what is proline isomerisation?
interconversion can be accelerated by peptidyl propyl isomerase (PPI) enzymes
- helps transformation from trans to cis
- can shif conformation
- involved in protein folding and regulation
what is N linked glycosylation?
- Asparagine = Asn = N
- N glycosylation is occurring on asparagine residues
what is glycosylation?
- have a protein in with a lipid chain
- on the cytolasmic side it pick up 2-N-acetyl-glucosamine residues and 9 mannose residues
- it then flips across the membrane
- in the ER lumen gets 3 glucose added
how are glucose residues are involved in quality control?
- help determine if a protein is folded correctly
- unfolded proteins retain a glucose that binds to ER chaperones, calnuxin and calreticulin, retaining them in the ER
- glucose group is added by glucosyl transferase
- folded proteins have glucose removed and allowed exit from the ER
how do prtoeins exit the ER?
use Sec61
what happens if folding fails?
proteins are retro-translocated into the cytosol and degraded by the proteasome
when is UPR triggered?
triggered by ER chaperones when unfolded proteins accumulate in the ER
what is the cause UPR?
the expression of a mutant protein causing disease
how does UPR work?
- triggers the upregulation of chaperone expression
- increased from the ER and proliferation of the ER
- prolonged UPR leads to cell death
how do the proteins leave the ER?
leave the ER in COPII coated transport vesicles
what do the soluble cargo proteins do?
- has an exit signal
- acitvely packaged into COPII
- pinch off ER to form a vesicle
what is the role of the exit signal?
- it binds a receptor
- receptor than binds to cytosolic proteins
- concentrates receptor into budding vesicle
what is the assembly of the coat initiated by?
- Sec12 binding to Sar1
- Sar1 exchanges GDP for GTP
