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DR. LINGWOOD:
In these cells instead of going through
this retrograde pathway, VT1 is internalized
again through Clathrin coated pits, but it's
internalized through this other pathway, which
I've drawn here on the right, which is the
degradation pathway. This is the pathway by
which cells make proteins and this is how they
degrade them through endosomes and lysosomes.
And so in these cells, monocytes
simulated by verotoxin, the VT is internalized
into endosomes and lysosomes. And it seems that
the toxin does translocate out into the lysosomes
and into the cytosol.
So now we have a third pathway,
too, down this way. Still, the two retrograde
transport pathways and now a third lysosome or
endosome pathway. And this is all mediated by
Gb3.
It turns out that the cells
that target the toxin this way, the monocytes
which produce cytokines which stimulate Gb3
synthesis in epithelial cells, their Gb3 on the
cell surface is organized differently than this
cell that targets this retrograde transport
pathway.
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