Transcripts
DR. LINGWOOD:
The other part of the puzzle is
what happens once the toxin gets inside the
cell. So verotoxin binds to Gb3 on the cell
surface here and the major internalization
pathway is through clathrin coated pits, and its
endocytosed into vesicles which then are
transported to what is called the Golgi complex
which is where glycolipids are synthesized. The
dogma is that from this compartment or from some
compartment; maybe these vesicles, the toxin
translocates into the cytosol where it inhibits
protein synthesis.
That may happen in some cases,
then this is the site of protein synthesis
inhibition - in the cytosol. I don't think that
this is a major player in the pathology of
verotoxin. What you see is that most of
the toxins either stays in the Golgi or
in the very sensitive cells, but it
goes on, and I will show
you, to target the ER (endoplasmic reticulum) and
some actually gets into the nucleus. And I
think that is the most important target.
There are two routes to go
here. One, as I said, through clathrin coated
pits. Verotoxin 1 goes through this way, but it
can also go through this other pathway, which is
called caveoli, but I won't go into this now.
It's very complicated entering vesicles which
fuse down here at the ER. VT2 does not go
this way, it only goes this way.
So maybe this now is not such a
pathogenic pathway as it is in some cells. The
use of these pathways is cell type specific, as
I will show you in a minute.
