ER and Golgi

Question 1

What are the general functions of ER and Golgi

Answer 1

ER - cotranslational tranlocation, polypeptide processing, secretion
Golgi - Transport and Processing

Question 2

Describe rER and contents

Answer 2

Single bilayer, cisternae, studded with ribosomes and ribophorin. Produces proteins destined for ER, organelles, secretion. Lumen contains enzymes and chaperones. Monitors assembly, retention, and degradation of proteins. More prominent in secretory cells

Question 3

Describe sER and contents

Answer 3

Network of membranous sacs continuous with cisternae. Involved in steroid hormone synth, detox, PL and lipoprotein synth, muscle contraction and relaxation (sarcoplasmic retic - Ca), glycogen degradation and gluconeogenesis ( GGP is an sER membrane protein and removal of P results in free glucose)

Question 4

Describe rER protein capture and transport targets

Answer 4

ER captures protein with ER signal sequence during synthesis in cytosol. Transmembrane proteins to PM, Organelles, or ER. Soluble to ER lumen to secretion or organelles.

Question 5

Describe cotranslational translocation

Answer 5

Proteins with ER signal sequence bind to SRP which binds to SRP-R on ER therefore binding ribosome to translocon. SRP complex displaced and polypeptide run through ER complex. BiP (Binding protein) chaperone pulls poly in while signal peptidase cleaves signal if at N-terminal

Question 6

What are the classes of transmembrane proteins

Answer 6

1. Single Pass type 1 - N term sig sequence and additional alpha helical stop region which embeds protein in membrane while N term inside and cleaved
2. Single pass type 2 - Internal signal sequence leading to two orientations of N terminal
3. Multipass - multiple internal stop and start sequences therefore many alpha helix across membrane

Question 7

What are the proteins involved with protein folding

Answer 7

1. Protein disulfide isomerase (PDI) - oxidizes free SH groups to form S-S cysteines
2. Chaperones - BiP, Calnexin, Calrecticulin: prevents aggregation and helps fold correctly, 2nd chance prior to degrade

Question 8

Describe Glycosylation

Answer 8

Premade Oligo (14 sugars: Nacyl glu, mannose, glucose) assembled and transferred to polypeptide by Dolichol (memb bound lipid) at NH2 of Asp
When folded properly, 4 sugars cleaved (3 glucose, 1 mannose) and processing continues in golgi

Question 9

What are the further modifications in golgi to sugars

Answer 9

1. Further N-linked trimming and/or addition of monosaccs

2. O-linked glycosylation: sugars to OH of selected Serine or Threonine

Question 10

What are Lipid anchors

Answer 10

GPI to lipid rafts

Question 11

Describe Degradation

Answer 11

Cant be fixed with chaperons, ejected though translocon, deglycosylated and ubiq. Taken up by proteosome and degraded to AA (non lysosomal degrade)

Question 12

What are the protein coats related to ER and Golgi and direction

Answer 12

COP 2 ER to golgi COP 1 golgi to ER

Question 13

What are the default signals for cytosolic proteins

Answer 13

NLS to nuc, SKL to peroxisome, mt signal

Question 14

What are the default signals for ER proteins

Answer 14

Default path is to PM or Secreted

KDEL (s) to ER, KKXX (t) to ER, M6P to lys

Question 15

What occurs when KDEL or KKXX signals reach golgi

Answer 15

KDEL seq to K-R to aggregation of COP 1 to vesicle to ER

KKXX doesnt need receptor as its transmemb

Question 16

Describe the packaging process

Answer 16

1. C to C-R
2. C-R concentrates in membrane
3. C-R to adaptin to COP coat (triggered by ARF-GTP)
4. Ves buds and pinches off
5. ARF hydrolysis leads to disassemble of coat exposing v-snares
6. fusion of v and t snares

Question 17

What are the functions of golgi

Answer 17

Major site of carb synth, addition of oligo to protein and lipids (cis side), sulphate on trans side.
Sorts and dispatches proteins and lipids form ER (trans)
M6P on cis side

Question 18

Describe theories on protein movement in golgi

Answer 18

1. Vesic transport of proteins btwn stages

2. Cisternal maturation when enzymes are transported

Question 19

Describe Cystic Fibrosis

Answer 19

Mutation in CFTR (F508) incorrectly folded so is degraded

Question 20

Describe Hypercholestrolemia

Answer 20

LDL-R mutation leading to CHD, arteriosclerosis, Xanthomatin, corneal arcus

Question 21

What is I cell disease

Answer 21

Mutation of M6P leading to waste accumulation