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#mannose-6-phosphate

3 public questions tagged with this topic.

Cell Organelles

Proteins destined for lysosomes are tagged with:

Lysosomal hydrolases require segregation from secretory proteins to avoid uncontrolled extracellular degradation. Selectivity conferred by addition of mannose-six-phosphate recognition marker in Golgi apparatus. In cis-Golgi UDP-GlcNAc phosphotransferase complex recognizes common conformational surface formed by lysine residues on hydrolases absent from secretory proteins, transferring N-acetylglucosamine-one-phosphate to C6 of mannose residues on high mannose N-glycans creating phosphodiester intermediate. Second enzyme GlcNAc-one-phosphodiester alpha-N-acetylglucosaminidase in trans Golgi re

Ref: Kornfeld & Mellman; M6P receptors TGN sorts hydrolases to endosomes, I-cell disease marker.

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Protein Sorting and Trafficking

What type of signal directs proteins from the Golgi to lysosomes?

Soluble acid hydrolases that degrade macromolecules inside lysosomes must be diverted from default secretory flow that would otherwise release them extracellularly. In cis-Golgi, UDP-GlcNAc: lysosomal enzyme N-acetylglucosamine-1-phosphotransferase, itself activated by Site-1 protease cleavage, adds GlcNAc-1-phosphate to carbon-6 hydroxyl of selected mannose residues on N-linked high-mannose oligosaccharides of hydrolase precursors arriving from ER. A second enzyme, uncovering enzyme, removes GlcNAc leaving mannose-6-phosphate monoester exposed. In trans-Golgi network, two mannose-6-phosphate

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 13: Mannose-6-Phosphate Tagging for Lysosomal Targeting.

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