Targeting to Lysosomes

Question 1

Lysosomes
distinct properties

Answer 1

Stomach of the cell
-Part of HP
-Acidic at pH 5 because of a proton pump

Question 2

2 Vesicular trafficking pathways

Answer 2

1. (Entering) Endocytosis AP-2 and clathrin
2. (Leaving) TGN to endosomes GGA and clathrin

Question 3

Endosomes

Answer 3

Point of convergence of for endocytic and biosynthetic pathway

Question 4

Mannose-6-Phosphate

Answer 4

Sorts lysosomes

Question 5

Main signal for sorting to lysosome, recognized by, and how are they generated

Answer 5

M6P modification is recognized by M6P receptor (MPR). Mannosylated precursor have phospho-GlcNAc added during cis-Golgi and uncovered at TGN

Question 6

I-cell patients lack what
how is this resolved

Answer 6

They lack GlcNAc phosphotransferase resulting for their lysosome enzymes to be secreted.
They add exogenous M6P-modified lysosomal enyzmes. They found that 10% of CI-MPR are in the cell surface to salvage secreted lysosomal enzymes.

Question 7

GlcNAc phosphotransferase

Answer 7

Adds GlcNAc-P to lysosomal enzymes,
Recognizes UDP-GlcNAc and signal patch of lysosomal enzyme

Question 8

Signal patch sufficient?

Answer 8

they used cathepsin D and a secreted protein, pepsinogen that is not phosphorylate and made a hybrid of the signal patch. pepsinogen had a similar 3D structure as CatD and was phosphorylated.

Question 9

MPR and how do they release their cargo

Answer 9

MPR bind M6P packaged in tor clathrin-coated vesicles delivered to early endosomes. They release their cargo because of the drop in pH at endosome. MPR are recycled back to TGN

Question 10

2 types of MPR

Answer 10

CI-MPR (300kda)
CD-MPR (46kDa)

Question 11

2 experiments that found CI-MPR to be at the cell surface

Answer 11

1. They inhibited CI-MPR and found lysosomal enzymes to be secreted