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Describe anterograde/retrograde transport.
(locations and coat proteins involved)

Anterograde - RER -> cis Golgi (forward), COPII
Retrograde - cis Golgi -> RER (backwards, COPI, proteins that escape the ER are transported back to the Golgi


How does a missorted protein in cis-Golgi return to the RER?

The missorted protein contains a KDEL peptide sequence which binds to the KDEL receptor. Vesicle forms -> RETROGRADE TRANSPORT


Describe the 2 models of transport through the Golgi complex.

- each Golgi part is stationary and vesicles transport the protein between stacks
- glycosylation occurs at each stack
- each vesicular stack matures into the next one
- no vesicular transport
- only retrograde transport
- late Golgi stage fragments into vesicles


Give the 5 locations where proteins can end up after being trafficked by the trans Golgi.

- lysosomes
- endosomes
- retrograde transport (vesicles)
- constitutive delivery of proteins to plasma membrane (happens all the time)
- periodic delivery to PM


Describe the process of transporting a protein to lysosomes.

glcNAc phosphortransferase transfers a phosphorylated glcNAc molecule to a carbon 6 atom of a mannose sugar on lysosome
phosphodiesterase cleaves glcNAc molecule leaving a phosphate group attached to lysosome


Describe the transport of the lysosome enzyme to the actual lysosome following the attachment of glcNAc.

- Man-6-pho added to lysosomal enzyme
- binds to receptor
- Clathrin coat formation and budding
- uncoating
- fusion w/ late endosome
- release from receptor
- dephosphorylation of glcNAc of lysosome
- fusion with lysosome
- recycling of coat proteins and receptor (to PM)
- phosphorylated lysosomal proteins can also be endocytosed through the plasma membrane


Give the overall route taken to direct a lysosomal enzyme to the lysosome.

RER -> cis/medial/trans Golgi -> Late endoscopes -> Lysosomes


On a molecular level, what occurs in I-cell disease?

- formation and attachment of Man-6-P to lysosomal enzymes is disrupted
- are not directed to lysosomes
- lysosomes contain high proportions of glycolipids and glycoaminoglycans because no enzymes are present to break them down
- lysosomes missing around 8 different acid hydrolases
- high proportions of lysosomal enzymes in blood and urine


Describe the 5 different ways on endocytosis.

- macro pinocytosis
- clathrin dependent
- caveolin dependent
- Cathrin/caveolin independent


What does receptor-mediated endocytosis depend on?

Clathrin being used as the coat protein


What 4 things does the AP (adaptor protein) complex bind?

- receptors for soluble cargo proteins
- clathrin
- membrane
- factors for vesicle formation and release


What role does dynamin play in vesicle formation?

Allows the vesicle to be pinched off via GTP hydrolysis


Describe the mode of action of pH dependent release of an LDL particle.

outiside the cell, pH = 7 therefore LDL binds to receptor
in endosome, pH = 5 therefore LDL dissociates from receptor and receptor is recycled back to PM


What is the cause of familial hypercholesterolaemia?

- mutations in LDL receptor
- leads to high concentrations of LDL in serum
- leads to fat deposition in certain cell types (-> Xanthomas (accumulation in skin and tendons) and atheromas)