Secretory Pathway I and II

Question 1

3 mechanisms of protein movement b/w compartments

Answer 1

1. ) Gated transport between the cytosol and nucleus
2. ) TM transport across a mem from cytosol into an organelle through translocators (e.g. protein synthesis and mitochondrial transport)
3. ) Vesicular transport b/w comparemtns

Question 2

Major organelles of exocytosis

Answer 2

ER, golgi, PM, vesicles and tubules

Question 3

Six major fx. of ER

Answer 3

1. ) Syntehsis of lipids (mostly SER)
2. ) Control of cholesterol homeostasis (sensor and synthesis)
3. ) Storage of Ca (for rapid uptake/release)
4. ) Syntehsis of proteins on RER
5. ) Co-translational folding of proteins & early posttrans modifications
6. ) quality control

Question 4

Co-translational translocation

Answer 4

mRNA bound to ribo floats around until SRP finds it and brings it to the membrane (translocon)
This is so protein can be put INTO ER
Signal sequence is cleaved after ER entry.

Question 5

Diff ribos for ER and cytosol proteins?

Answer 5

Nope same ribo pool.

ER signal sequence on a newly formed polypeptide chain “directs” the engaged ribo to the ER mem.

Question 6

How does this ER direction work?

Answer 6

ER signal sequence on nascent polypep being synthesized. is recognized by SRP (which uses methionine for flexible binding)
SRP binds ribosome and peptide get TRANSLATION PAUSE by using GTP. It is brought to cytosolic face of ER.
SRP receptor binds, peptide transferred to translocon.
SRP detaches as GTP hydrolyzed. polypeptide chain enters the ER.
Continued elongation of peptide into ER.
Signal sequence cleaved.
Ribo dissociates. Is recycled.

Question 7

Translocon regulation

Answer 7

Closed. But regulation via riobosome at cytosolic face and chaperon Bip in the ER lumen.
After protein passes the translocon opens sideways so hydrophobic signal seq can leave and be degraded.
Bidirectional!
Misfolded proteins leave ER and degraded through translocon.

Question 8

Bip

Answer 8

regulates translocon in ER lumen.

Helps fold as protein enters. Disulfide isomerase (bonds).

Question 9

Type I membrane protein

Answer 9

1 TMD. amino terminal in ER terminal.
To get 1 TMD: mRNA has “stop transfer” signal, so it’s released by translocon and C-terminal end is then synthesized in cytosolic space.

Question 10

Type II membrane protein

Answer 10

Opposite orientation of type I.

Question 11

Multiple TM domain proteins.

Answer 11

They have internal stop/start seq.

Syntehsize from start to stop into lumen, then transfer to cytosol synthesis.

Question 12

Sugar additions

Answer 12

Many get asparagine added to N terminal. N-linked glycosylation.
More complex glycosylation in golgi.

Question 13

Why add sugar?

Answer 13

It keeps proteins from aggregating when hydrophobic domains are exposed.
Glucose residues also monitor unfolded proteins.

Question 14

ER to Golgi transport

Answer 14

ER and Golgi NEVER fuse.

Move cargo via vesicles which move on tubules, requires cargo, coat, and mem proteins/lipids destined to move.

Question 15

Coat proteins made of…

Answer 15

soluble cytoplasmic lipids/proteins at site of vesicle formation. Can move back (golgi to Er) or forward (ER to golgi).
Re-utilization: SCAp and SREBP

Question 16

COPII

Answer 16

ER to Golgi (forward)

Question 17

COPI

Answer 17

Golgi to ER (backwards)

Question 18

Clathrin

Answer 18

Golgi to PM (mem to lysosome). all around.

Question 19

Recruitment into vesicles?

Answer 19

Specific AA motifs on cytosolic side of the mem proteins are recognized by the adaptor proteins for recruitment into the vesicles

Question 20

Major golgi fx.

Answer 20

sphingolipid (complex) synthesis
Post-translational modification of proteins/lipids
Proteolytic processing
Sort proteins/lipids for compartments

Question 21

Compartments of golgi

Answer 21

Cis (closest to ER)
medial
trans
trans golgi network (vesicles bud form here and are sorted). 
All have diff enzymes with diff. fx.

Question 22

Secreted vesicles pathways?

Answer 22

1. ) Constitutive (secreted ASAP)

2. ) Regulated (secreted only with proper signal).