Lecture 14 - Protein trafficking in epithelia 3 Flashcards
What is required to specifically traffic apical proteins?
Binding proteins as trafficking to apical membrane is saturable
What are the 3 models for protein exocytosis in epithelial cells?
- Direct route
- Indirect route
- Random sorting
What is the direct route model for protein exocytosis in epithelial cells?
Proteins are sorted in TGN into apical or basolateral bound vesicles. Once in vesicles the proteins go straight to their appropriate membrane
What is the in direct route model for protein exocytosis in epithelial cells?
- All proteins exocytosed to one membrane
- Proteins retrieved from membrane (endocytosis) and trafficked to endosome
3a. Apical proteins trafficked to apical membrane
3b. Basolateral proteins trafficked to basolateral membrane
What is the in random sorting route model for protein exocytosis in epithelial cells?
- Proteins trafficked to either membrane randomly
- Proteins retrieved from membrane (endocytosis) and trafficked to endosome
3a. Apical proteins redirected to apical membrane
3b. Basolateral proteins redirected to basolateral membrane
What is the exocyst believed to aid in?
The exocyst is believed to aid in the trafficking of basolateral proteins via the lateral membrane
Which statement about protein sorting and targeting in epithelia is CORRECT?
A. The exocyst is the site for delivery of proteins to the basolateral membrane.
B. Experimental evidence shows that the trans-Golgi network can sort apical and basolateral proteins into separate vesicle populations.
C. In the indirect sorting pathway all proteins are first delivered to the same membrane domain.
D. All of A, B and C are correct
D. All of A, B and C are correct
Endocytosis of transmembrane proteins occurs through interaction with the AP2 complex BECAUSE the transmembrane proteins contain amino acid sequences such as YXXϕ.
A. Both statements true and causal.
What specfic adaptin is found in the plasma membrane clathrin-coated pits?
AP2
What are endocytosis motifs bound by?
clathrin-binding adaptins
What four subunits make up AP2?
α and β adaptins
μ2 adaptin
σ2 subunits
What does the α and β adaptin subunit of AP2 bind to?
Clathrin
What does the μ2 adaptin subunit of AP2 bind to?
YXXϕ
What are examples of tyrosine based amino acid motifs?
YXXϕ
NPXY
What is an example of hydrophobic amino acid motifs?
LL
What happens to basolateral transferrin receptor (TfR) once endocytosed?
Once ligand-bound transferrin is endocytosed to
basolateral sorting endosome, it is trafficked on to common endosome. From here the TfR is either recycled back to basolateral membrane or trafficked through the late endosome to the lysosome for degradation
What is the endocytosis and recycling or
degradation of apical ENaC?
Once ENaC is ubiquitinated and endocytosed, it is trafficked through apical sorting endosome to the common endosome. From here either:
* Ubiquitin removed and recycled back to apical membrane
* Ubiquitin remains and is trafficked to late endosome and onto the lysosome for degradation
What is the steps of endocytosis in epithelia?
- Protein is endocytosed to applicable sorting endosome (apical protein to apical sorting endosome)
- Endocytosed material (apical and basolateral) goes to the common endosome
- Proteins recycled back to corresponding membrane
How are apical proteins believed to be recycled back to the apical membrane?
Via an apical recycling endosome
What amino acid motifs are found on ENaC subunits?
ENaC subunits have YXXϕ motifs and are monoubiquitinated
What amino acid motifs are found on CFTR?
CFTR has YXXϕ and LL motifs
What amino acid motifs are found on Na+/K+ ATPase subunits?
Na+/K+ ATPase subunits have YXXϕ and LL motifs
What is the transcytosis of the immunoglobulin A receptor (IgAR)?
- IgAR endocystosed from basolateral
membrane and trafficked to basolateral sorting endosome
2 & 3. Trafficked on to apical recycling endosome through common endosome - IgAR exocytosed to apical membrane
