membrane trafficking in disease

Question 1

COPII vesicle GTPase + cargo

Answer 1

Sar1 GTPase
new proteins

Question 2

COPI vesicle GTPase + cargo

Answer 2

Arf1
retrieved + new protein

Question 3

clathrin vesicle GTPase + cargo

Answer 3

ARf1/dk
lysosomal proteins
endocytosed

Question 4

role of adaptor proteins

Answer 4

• Recognise and select cargo ensuring specificity
  
  • concentrate cargo into vesicles
• Link the coat to the ER membrane
• Adaptors recognise motifs in the cytoplasmic domains of membrane proteins

Question 5

where are adaptor proteins 1,2 and 3 found

Answer 5

• AP1 found on endosomes and golgi network to form transport vesicles
• AP2 found in clatherin coated vesicles
• AP3 found in TGN on lysosomal cells

Question 6

difference between adaptor proteins

Answer 6

→ similar structure but are very specific for location and cargo ie. never end up in wrong place

Question 7

adaptor protein 2 structure

Answer 7

• alpha, beta, gamma, o
• appendages interact with many proteins
• subunit b2 bind clatherin proteins
• o2 recognise signals

Question 8

what is CLSD

Answer 8

• issues with ossification of bone and fontanelles do not fuse
• hyperpigmentation
• musculoskeletal issues
• single mutation in sec23a
  → issue with packaging cargo into cop2 vesicles
  → issue with forming cop2 vesicles

Question 9

how is packaging of large cargo managed

Answer 9

modifications of cop2 coat sort proteins into tubular structures

Question 10

what is the Rab protein family

Answer 10

• member of the Ras superfamily
• distinct subcellular localisation
• cycle between membrane and cytosol
• required for fusion and many other trafficking functions
• use balance of gefs and gaps to maintain status

Question 11

role of rabs in fusion

Answer 11

• docking vesicle
• recruited rab in gtp form recruits tethering protein that associates with organelles and allows rab to interact with one end of tether
• facilitates snare complex to form

Question 12

Rab cascades function

Answer 12

allow movement of cargo between organelles
Rab5 = delivers content to late endosomes -> Rab 6 etc

Question 13

role of Rabs in disease

Answer 13

Charcot-Marie-Tooth Disease
- neurodegeneration
- missense in rab7 = overactive
- reduces autophagy
- premature degredation of neurotrophine receptors

Harnessing of rabGEFs by pathogens