cell biology 3 Flashcards
what is the eukaryotic secretory pathway
1) protein translocation
2) endoplasmic reticulum
3) Golgi
4) late endsome —> lysosome
5) late endsome —-> early endosome—–> cell exterior
6) Golgi —> cell exterior
7) secretary vesicles —> cell exterior
what is the N-termial signal sequence
- target proteins to ER
features: - positive N-region
- hydrophobic H region
- signal patern C region
how does co-translation of proteins occur in eukaryotes
1) SRP binds to the signal sequence and translation pauses
2) SRP guides the signal sequence to the SRP receptor at the ER
3) SRP and SRP receptor released
4) translation drives translocation
- signal sequence cleaved by signal peptidase
- ribosome components recycled
what happens in post-translational targeting in ER in humans
- little is known
- most secretory proteins co-translationaly targeted
- most work done by yeast
what does yeast require in post-translational targeting
- Sec61 complex - core translocon
- Sec62/63 complex - substrate binding and recognition
- BIP - binding protein - ATPase chaperone in the ER
- substrates - secretory proteins, single pass and double pass membrane proteins
what is the ER modifications
- N-linked glycosylation
- Protein folding with chaperones
- Proteolytic cleavage
- Protein oligomerisation
- Disulphide bonds form (Protein disulfide-isomerase, PDI)
what are the golgi modifications
- O-linked glycosylation
- Modification of glycosylations
what happens if a protein is misfolded
- recognised by calnexin
- exported to cytosol
- glycosylations removed
- poly-ubiquitnated
- degraded at the proteasome
what happens when there is excess misfolded proteins
- simulated ER membrane proteins:
S/T Kinase Inositol-Requiring enzyme 1 (IRE1)
Protein kinase R-like ER kinase (PERK)
Activating transcription factor 6 (ATF6 - simulates the unfolded protein response
what is the unfolded protein response - UPR
- reduced translation
- promotes expression of chaperone genes
- can lead to apoptosis - regulated cell death
what makes a protein misfolded
- mistargeted
- degraded
-unpregulated - down regulated
- unstable
-dysfunctional
what types of cystic fibrosis are caused by a misfolded protein
class 3 - mistargeted/ degraded
class 4 - dysfunctional
class 6 - unstable
what causes insulin resistant syndrome
- INSR defects
- reduced child weight gain and growth
what causes autosomal dominant deafness type 2A
- KCNQ4 mutations
- increased function
- decreased function - less membrane
what is a COPII vesicle
- coated vesicle carrying cargo from ER to golgi
how is a COPII vesicle formed
1) ) Sar1-GDP binds to a Sar1-GEF at the ER
2) Sar1 binds GTP → Sar1 exposes amphiphilic helix
3) Sar1 inserts into ER membrane
4) Sar1 binds COPII adaptor coat proteins (Sec23/24)
5) COPII coat protein complex (Sec13/31) binds
6) Transmembrane proteins recruited → membrane deforms
7) Membrane pinches off