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Vol. 11, Issue 5, 1829-1843, May 2000
and
*Department of Biochemistry, Sciences II, University of Geneva,
1211-Geneva-4, Switzerland; In the present study, we show that in human endothelial cells the
tetraspanin CD63/lamp3 distributes predominantly to the internal
membranes of multivesicular-multilamellar late endosomes, which
contain the unique lipid lysobisphosphatidic acid. Some CD63/lamp3 is
also present in Weibel-Palade bodies, the characteristic secretory
organelle of these cells. We find that CD63/lamp3 molecules can be
transported from late endosomes to Weibel-Palade bodies and thus that
CD63/lamp3 cycles between endocytic and biosynthetic compartments;
however, movement of CD63/lamp3 is much slower than that of P-selectin,
which is known to cycle between plasma membrane and Weibel-Palade
bodies. When cells are treated with U18666A, a drug that mimics the
Niemann-Pick type C syndrome, both proteins accumulate in late
endosomes and fail to reach Weibel-Palade bodies efficiently,
suggesting that P-selectin, like CD63/lamp3, cycles via late endosomes.
Our data suggest that CD63/lamp3 partitions preferentially within late
endosome internal membranes, thus causing its accumulation, and that
this mechanism contributes to CD63/lamp3 retention in late endosomes;
however, our data also indicate that the protein can eventually escape
from these internal membranes and recycle toward Weibel-Palade bodies
to be reused. Our observations thus uncover the existence of a
selective trafficking route from late endosomes to Weibel-Palade bodies.
Division of Clinical
Biochemistry, Centre Médical Universitaire, 1211-Geneva-4,
Switzerland; Division of Angiology and Hemostasis,
University Hospital Geneva, 1211-Geneva-4, Switzerland; and
§Centre for Microscopy and Microanalysis, Department of
Physiology and Pharmacology, and Centre for Molecular and Cellular
Biology, University of Queensland, Queensland 4072, Australia
Corresponding author. E-mail
address: jeangruenberg{at}biochem.unige.ch.
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