Lysosomal Storage Disease

Question

In my biochemistry class today we did a problem detailing two lysosomal storage diseases.

In the first scenario, a cell line for I-cell disease can synthesize lysosomal hydrolases that are perfectly functional which are then secreted outside of the cell instead of being sort to the lysosome. However there is a mutation that inhibits the the kinase domain that normally phosphorylates Mannose-6-Phosphate (M6P), so there is no M6P-labeling in these cells.

In the second scenario, a cell line for Hurler's disease has a mutation that eliminates one lysosomal glycosidase so that it cannot degradte certain classes of oligosaccharides. This results in the cells of this mutant cell line to have engorged / bloated lysosomes.

Now when these two cell lines are co-cultured in the same flask, it is observed the I-cell culture correctys the defect in the Hurler cell culture, while the Hurler cell culture was not able to correct the defect in the I-cell culture.

My question is how can this phenomenon be explain? And why are the Hurler cells still growing?

Answer 1

I-cells produce the normal functional lysosomal hydrolases, however they are secreted outside of the lysosome.

The Hurler cells lack a functional lysosomal hydrolase to degrade the certain oligosaccharides.

When the two cell lines are mixed together in the same media, through non-specific endocytosis, the Hurler cells will simply arbitrarily want to endocytose things such as nutrients from the media into the cell, and some of the times, the Hurler cells may endocytose the functional enzymes secreted outside of the extracellular matrix / membrane from the I-cell.

Thus, the Hurler cell's lysosomal contents can then be degraded to some extend and restore the defect exhibited in normal Hurler Cells.