Question

Describe intracellular trafficking of CI-M6PR, with names of specific molecules involved in the process, and its role in mechanism underlying I-cell disease.

Answer 1

The CI-M6PCR is involved in targetting the lysosomal enzymes. CI-M6PCR binds to any lysosomal enzyme that has mannose 6-phosphate signal. Generally, lysosomal enzymes are synthesised in rough endoplasmic reticulum where they got oligosaccharide composed of a Glc₃Man₉GlcNAc₂ tag. In cis golgi complex, the GlcNAcphosphotransferase enzyme adds a GlcNAc-1-phosphate residue onto the 6-hydroxyl group of a specific mannose residue to oligosaccharide to form mannose 6-phosphate GlcNAc. The enzymes are then targetted to the trans-Golgi network, where the GlcNAc has removed to expose the mannose phosphate signal. This mannose phosphate may here be recognised by the M6PCR after enzyme receptor binding lysosomal enzymes transported to the endosome. In endosomes, the receptors release the lysosomal enzymes out and the receptors are back transported to the trans-golgi network.

In I-cell disease the phosphotransferase enzyme is defective which make the lysosomal enzymes not to be detected by CI-M6PCR receptor, so instead of targeted to the endosomes, the secretory enzymes are secreted out. The lysosome without these enzymes cannot degrade materials in it, so the substances accumulated in the lysosomes resulting into Inclusion cells or I-cells.