Lecture 18 - The Endomembrane System II Flashcards
where do disulphide bonds form and what prevents remote cysteine residues from interacting to form these bonds:
Disulfide bonds form between cysteine amino acids & the reducing environment of the cytosol prevents remote cysteine residues from interacting and forming these bonds
how can you describe the ER lumen environment and what bonds does it allow to form?
ER lumen is an oxidative environment, so disulfide bonds can form
what is the name and type of enzyme that catalyses redox reactions that alter the position of disulphide bonds on proteins?
Protein disufide isomerase (PDI) is an ER lumenal oxidoreductase that catalyses redox reactions that alter the positions of disufide bonds on proteins
what is the process of protein disulphide isomerase altering disulphide bonds crucial for?
This process is essential for correct folding of proteins and for functionality of some lysosomal proteins and external domains of proteins
what happens to many proteins that enter the ER?
many proteins that enter the ER are glycosylated
how does glycolisation happen and where does it happen and why does it happen in this location?
glycolisation occurs in the ER lumen so only extracellular parts of the proteon are glycosylated
glycolisation works through the addition of an oligosaccharide to an asparagine (N) residue
what happens to improperly folded protein in the ER?
Improperly folded proteins held in the ER by chaperone proteins until they are properly folded….. or, if this doesn’t happen, degraded
what does the ER perform ‘quality control’ on?
the ER performs ‘quality control’ on protein folding
what happens to properly folded proteins in the ER?
properly folded proteins exported from he ER are transported to the golgi apparatus
what happens in the ER to allow for the translocating protein to fold?
In the ER hsp40 and hsp70 combines with a nucleotide exchange factor to ratchet in and enable the translocating protein to fold
what does unfolded protein in the ER trigger?
Unfolded proteins in the ER trigger production of chaperones and the expansion of the ER
what in the rER activates a transcription factor in the cytoplasm when bound to unfolded proteins?
transmembrane receptors in the membrane
the unfolded & folded rote in response flow diagram:
translocation of linear polypeptide chain into the ER → folding protein → aggregation (1) / successful fold (2)
(1) aggregation → unfolded protein response (repair) / degradation → autophagosome / hydrolysation through living ER via a proteasome
(2) successfully folded protein → vesicle forms
purpose of the smooth ER:
synthesises phospholipids, cholesterol & metabolises hormones and drugs
sarcoplasmic reticulum:
sarcoplasmic reticulum is the ER in muscle cells, it is a major store of calcium ions
how is the ER responsible when Ca2+ levels in the cytosol are low?
The ER contains several calcium channels, ryanodine receptors and inositol 1,4,5-trisphosphate (IP3) receptors (IP3R) that are responsible for releasing Ca2+ from the ER into the cytosol when intracellular levels are low.
what does the depolarisation of t-tubule membranes lead to?
Depolarisation of t-tubule membranes can lead to conformational changes in voltage-dependent Ca2+channels, such as dyhydropyridine receptors (DHPRs), which interact and leads to Ca2+ release.
how are the t-tubules arranged in the muscle cells?
the muscle cell membrane (sarcolemma) has t tubules that pass down into the muscle cell and go around the MYOFIBRILS
what do the t-tubules of the muscle cell actually do?
the t-tubules conduct impulses from the cell membrane down into the cell and to the special type of smooth ER that is found only in the muscle called the sarcoplasmic reticulum
t-tubule mechanism in muscle cells:
(1) action potential spreads along the surface membrane (sarcolemma) and the t-tubules - deep into the muscle
(2) the DHP receptor protein senses the membrane depolarisation, changes conformation and activates RyR (receptor found in sarcoplamsic reticulum)
(3) this causes the SR to release calcium ions which bind to troponin and activated the contraction process
what releases calcium ions in the muscle?
the sarcoplasmic reticulum
what is another very well known calcium release event?
the calcium ion release event that occurs at fertilisation following sperm entry
autophagy:
autophagy induction signals leads to the formation of a phagophore which is a ‘sequestering membrane’
there are then some ubiquination like reactions and LC3 conjugates which elongates the membrane
the cytoplasmic components and viruses and bacterium are then entrapped by the phagophore and at the end of elongation a double membrane vesicle is formed called a autophagosome
the autophagosome is then delivered to be fused with the lysosome to form an autoysosome which will degrade the components
how is the RER involved in protein folding?
the RER is involved in protein folding using chaperone proteins (BiP cycle and calnexin/calreticulin cycle)
glycolisation on asparagine residues (N) allows for what?
Glycosylation of proteins on Asparagine residues (N) and addition of disulfide bonds helps them to fold
