protein trafficking 3-26 Flashcards
Processes of integral membrane proteins
signaling, channels
3 types of protein membrane spanning domains
alpha helix, beta (antiparallel) barrels, alpha bundle
how do proteins get inserted into the membrane in the first place
n-terminal Signal Peptide contains hydrophobic aa’s that get recognized by Signal Recognition Particle (SRP) stopping translation, which conducts it to the SRP Receptor/Ribophorin of the ER, where it is cleaved and continues translating
Defect in Cystic Fibrosis
The CFTR (CF transmembrane contuctance regulator) is mutated, usually missing a phenylalanine (DF508)- causes ERAD to degrade functional Chloride ion channel
How does CF cause saltier sweat?
Usually CFTR in the gland reabsorb the NaCl, but in the case of CF are unable to because intracellular concentration of CL is high, not enough chloride channels
ASO
allele specific oligonucleotide test, uses radioactively labelled DNA to test for DF508 allele
3 symptoms of CF
excessive mucous in the lungs (bacterial infections, breathing, widening airways), dysfunctional secretion by the pancreas, salty skin
Molecular pathway that leads to CF
Mutant CFTR (DF508) gets help folding on extracellular component by chaperones Aha1 and Hsp90, but they remain bound too long and trigger ERAD pathway
ERAD
ER Associated Degradation- misfolded proteins are pulled from the membrane to the cytosol/proteasome, keeps bad proteins at bay unless ER stress, mutant protein occurs
UPR
Unfolded Protein Response- where levels of bad proteins rise, so translation rate decreases and transcription factors for ER stress machinery get upregulated
How is diabetes related to ER Stress
Stress on beta cells of the pancreas begin a downward spiral when ER becomes stressed, some of the cells die, which increases the stress load of the remaining cells until they follow suit
