protein sorting- late secretory pathway Flashcards Preview

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Flashcards in protein sorting- late secretory pathway Deck (15):

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

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


Clathrin-associated sorting proteins (CLASPs) mech

nucleation, invagination, scission


dynamin mech

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)


soluable lysosomal enzymes processed in



soluable lysosomal enzymes processed by

adding M6P residues


soluable lysosomal enzymes receptor

M6P residues recognized by M6P receptor in trans-Golgi


soluable lysosomal enzymes sent to

late endosomes, then lysosome


soluable lysosomal enzymes receptors recycled in

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


M6P mech in cis-Golgi

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


Trafficking of soluble lysosomal enzymes from the trans-Golgi network

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.


Proteolytic processing of proproteins in the constitutive pathways

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


Proteolytic processing of proproteins in the secretion pathways

precusors are cleaved at multiple sites.


receptor mediated endocytosis pathway for LDL mech

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


familial hypercholesterolemia (FH)

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


pH dep LDLR

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