Skip to content
Login Register

#lysosomal enzymes

3 public questions tagged with this topic.

Protein Sorting and Trafficking

Which signal is necessary for targeting soluble lysosomal enzymes?

Among diverse sorting determinants mannose-6-phosphate uniquely marks entire class of soluble lysosomal precursors enabling intracellular lysosome biogenesis. Newly synthesized acid hydrolases enter ER lumen, receive high-mannose N-glycans via oligosaccharyltransferase, fold with calnexin, move to cis-Golgi where Golgi-resident phosphotransferase adds M6P as phosphodiester then uncovered in TGN to yield exposed phosphate. Carbohydrate address recognized in TGN pH 6.7 by two M6P receptors both P-type lectins: 300 kDa cation-independent IGF2 receptor binding also IGF2 and 46 kDa cation-dependent

Ref: Lodish et al., MCB: Mannose-6-phosphate signal targets soluble lysosomal enzymes to lysosomes.

View Details
Protein Sorting and Trafficking

What happens if a mutation prevents phosphorylation of Mannose-6-Phosphate (M6P)?

Targeting soluble acid hydrolases to lysosomes hinges on carbohydrate tag mannose-6-phosphate discovered by fractionation. In cis-Golgi, UDP-GlcNAc:lysosomal enzyme GlcNAc-1-phosphotransferase alpha2 beta2 gamma2 recognizes structural patch including lysine residues clustered in tertiary structure on hydrolases like cathepsin B and adds GlcNAc-phosphate to terminal mannose of high-mannose N-glycans. Uncovering in TGN by NAGPA removes GlcNAc exposing M6P monoester capable of binding M6P receptors. M6P receptors divert enzymes from default secretory flow into clathrin-AP1 and GGA vesicles destin

Ref: Alberts et al., MBC: I-cell disease defective GlcNAc-phosphotransferase causes lysosomal enzyme secretion.

View Details
Protein Sorting and Trafficking

In which Golgi compartment does phosphorylation of lysosomal enzymes occur?

Soluble acid hydrolases acquire mannose-6-phosphate marker for lysosomal delivery through selective two-step modification restricted to Golgi apparatus, discovered by Kornfeld laboratory. Newly synthesized hydrolases enter ER, receive high-mannose N-glycans, fold with calnexin cycle, then travel to cis-Golgi network. There UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase alpha2 beta2 gamma2 hexamer encoded by GNPTAB and GNPTG recognizes conformational patch on hydrolases and transfers GlcNAc-1-phosphate to C6 hydroxyl of select mannose residues forming phosphodiester interm

Ref: Lodish et al., MCB, Chapter 14 Figure 14-21 Formation of M6P residues in cis-Golgi by phosphotransferase.

View Details