First published online July 31, 2003
Journal of Cell Science 116, e1704 (2003)
Copyright © 2003 The Company of Biologists Limited
Trypanosome invasion - a pincer movement?
Trypanosoma cruzi, the infectious agent in Chagas' disease,
invades cells by inducing exocytosis of lysosomes, which supply the membrane
that surrounds the phagocytosed invader. The process requires phosphoinositide
3-kinase (PI3K) and involves depolymerization of the host's cortical actin
cytoskeleton. Work by Barbara Burleigh and co-workers, however, indicates that
trypanosomes can use an alternative invasion route (see
p. 3611). Using
time-lapse fluorescence imaging and GFP fusion proteins to visualize the
process, they observe that more than half of all invading parasites are
internalized into plasma-membrane-derived structures at sites that lack
lysosomal markers but are enriched in lipids produced by PI3K. They
subsequently show that these compartments gradually acquire lysosomal markers
(residence in an acidic lysosomal compartment is a prerequisite for entry into
the cytosol) through a maturation mechanism distinct from classical phagosome
maturation. The authors then employ the inhibitor wortmannin to demonstrate
that, although both invasion pathways require PI3K, they do so at different
times: the enzyme is needed at a late stage during typical phagosome
maturation but much earlier on when plasma-membrane-derived compartments are
involved. Burleigh and co-workers suggest the early activation of PI3K could
be a consequence of specific interactions between parasite glycoproteins of
the trans-sialidase/gp85 family and host cell-surface receptors.
Related articles in JCS:
- Novel PI 3-kinase-dependent mechanisms of trypanosome invasion and vacuole maturation
- Aaron M. Woolsey, Lisa Sunwoo, Christine A. Petersen, Saskia M. Brachmann, Lewis C. Cantley, and Barbara A. Burleigh
JCS 2003 116: 3611-3622.
[Abstract]
[Full Text]
