The ER as a stress sensor and beyond the ER

Question 1

What are the five major interdependent strategies for ER selective transport

Answer 1

Cargo capture: receptor-mediated export of proteins from the ER to the Golgi
complex in coatamer protein II (COPII) vesicles.
Bulk flow: some proteins and lipids are included in COPII vesicles by
default
Retention: prevents proteins from entering the transport vesicles
Retrieval: retrograde transport from the ER-Golgi intermediate
compartment (ERGIC) /early Golgi back to the ER
ERAD: cytosolic elimination of ER proteins that fail quality control

Question 2

Describe the process of cargo capture

Answer 2

In the ER, secretory cargo is loaded into COPII
transport vesicles at ER exit sites (ERES).
This requires export signals in fully folded
client proteins and cargo receptor proteins ( )
in the vesicle membrane.
COPII vesicles fuse to form the ER-Golgi
intermediate compartment (ERGIC).
When COPII vesicles are close to the cis-Golgi
membrane, they shed their coats - COPII
components are recycled for use in other
vesicles.
The receptors usually return to the ER by
retrieval pathways

Question 3

Describe the process of bulk flow and retention

Answer 3

Export by bulk flow does not require receptors
or export signals. Some soluble and
membrane proteins (and membrane lipids)
enter COPII vesicles by default.
There is a biotechnological use: foreign
proteins directed into the ER are often secreted
into the growth medium as soluble proteins
that are relatively easy to purify.
Retention: some proteins ( ) are selectively
excluded from COPII vesicles.

Question 4

Describe retrieval and retrograde transport COP1

Answer 4

For retrograde transport from ERGIC and the
cis-Golgi, COPI coated vesicles retrieve
transport machinery, cargo receptors, lipid
membrane, and escaped ER-resident
proteins.

Question 5

Describe the ER as a stress sensor

Answer 5

The protein folding capacity of the endoplasmic reticulum (ER) is tightly regulated
by a network of signalling pathways - the unfolded protein response (UPR).
• UPR sensors monitor the ER folding status of proteins in the ER.
• Following sensing, the UPR adjusts the folding capacity of the ER according to need.

Question 6

Describe what Ire1 is and its mechanism

Answer 6

Ire1 is a universal stress sensor in eukaryotes
Activates through autophosphorylation activating RNAse activity increasing ER stress
Activated Ire1 splices a specific RNA

Question 7

Describe difference between PERK and Ire1

Answer 7

IRE1 activation leads to specific splicing and production of transactivators of transcription.
However, PERK activation leads to interference with translation

Question 8

How is PERK activated?

Answer 8

No ER stress, BiP is bound to PERK
PERK auto transphosphorylates. Activated PERK phosphorylates eIF2α
Activated eIF2α reduces translation globally – and this reduces protein expression and relieves stress

Question 9

TIP

Answer 9

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