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Vol. 11, Issue 12, 4205-4216, December 2000
and
*Institute for Cancer Research, The Norwegian Radium Hospital,
Montebello, 0310 Oslo, Norway; We have here studied the role of cholesterol in transport of ricin
from endosomes to the Golgi apparatus. Ricin is endocytosed even when
cells are depleted for cholesterol by using methyl-Structural Cell Biology
Unit, Department of Medical Anatomy, The Panum Institute, University of
Copenhagen, DK-2200 Copenhagen N, Denmark
-cyclodextrin (mCD). However, as here shown, the intracellular transport of ricin
from endosomes to the Golgi apparatus, measured by quantifying sulfation of a modified ricin molecule, is strongly inhibited when the
cholesterol content of the cell is reduced. On the other hand,
increasing the level of cholesterol by treating cells with mCD
saturated with cholesterol (mCD/chol) reduced the intracellular transport of ricin to the Golgi apparatus even more strongly. The intracellular transport routes affected include both
Rab9-independent and Rab9-dependent pathways to the Golgi apparatus,
since both sulfation of ricin after induced expression of mutant Rab9
(mRab9) to inhibit late endosome to Golgi transport and sulfation of a modified mannose 6-phosphate receptor (M6PR) were inhibited after removal or addition of cholesterol. Furthermore, the structure of the
Golgi apparatus was affected by increased levels of cholesterol, as
visualized by pronounced vesiculation and formation of smaller stacks.
Thus, our results indicate that transport of ricin from endosomes to
the Golgi apparatus is influenced by the cholesterol content of the cell.
Corresponding author. E-mail
address: ksandvig{at}radium.uio.no.
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