protein sorting- late secretory pathway

Question 1

Vesicle-mediated protein trafficking from the trans-Golgi network (5)

Answer 1

Retrograde transport vesicles, Directly to lysosome. To late endsome and then to lysosome (with clathrin), Constitutive secretory vesicles, Regulated secretory vesicles

Question 2

Clathrin-associated sorting proteins (CLASPs) mech

Answer 2

nucleation, invagination, scission

Question 3

dynamin mech

Answer 3

late stage of budding, dynamin polymerizes around the neck proteins, hydrolyze GTP (drives confirmational change to stretch vesicle neck), clathrin/AP vesicles lose coat after pinching off (Hsp70 used to drive depolymeration of coat proteins)

Question 4

soluable lysosomal enzymes processed in

Answer 4

cis-Golgi

Question 5

soluable lysosomal enzymes processed by

Answer 5

adding M6P residues

Question 6

soluable lysosomal enzymes receptor

Answer 6

M6P residues recognized by M6P receptor in trans-Golgi

Question 7

soluable lysosomal enzymes sent to

Answer 7

late endosomes, then lysosome

Question 8

soluable lysosomal enzymes receptors recycled in

Answer 8

receptors dissociate in late endosome, recycled into Golgi or plasma mem

Question 9

M6P mech in cis-Golgi

Answer 9

GlcNAc phosphotransferase add phosphorylated GlcNAc to core Man8(GlcNAc), phosphodiesterase removes GlcNAc.

Question 10

Trafficking of soluble lysosomal enzymes from the trans-Golgi network

Answer 10

M6P receptor binds to M6P at pH6.5 and release at pH lower than 6 (late
endosome: pH5.0-5.5), A phosphatase in late endosome removes phosphate group.

Question 11

Proteolytic processing of proproteins in the constitutive pathways

Answer 11

precursor proteins are cleaved at di-basic recognition sequence (Arg-Arg or Lys-Arg)

Question 12

Proteolytic processing of proproteins in the secretion pathways

Answer 12

precusors are cleaved at multiple sites.

Question 13

receptor mediated endocytosis pathway for LDL mech

Answer 13

N-terminal segment of LDLR binds to apoB-100, a NPXY sorting signal in LDL receptor binds to AP2, apoB-100 (surface) is hydrolyzed by lysosomal proteases, cholesteryl esters (core) hydrolyzed by lysosomal cholesteryl esterases

Question 14

familial hypercholesterolemia (FH)

Answer 14

many forms, common/well-studied one is where NPXY sorting signal mutated, cannot bind to AP2 complex, cannot link clathrin/AP2 coats to LDLR, cannot internalize LDLR into coated pits

Question 15

pH dep LDLR

Answer 15

low pH (late endosome)= arm is in
high pH (call surface) = arm is out, can bind to LDL