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Marilyn Parsons , Ph.D.
Protein Targeting to the Toxoplasma
gondii Plastid
The protozoan parasite Toxoplasma gondii is both an important pathogen in its own right and a useful model to study apicomplexan cell biology. Like the malaria parasites,
T. gondii possess an unusual organelle, the apicoplast, which contains a genome reminiscent of those found in chloroplasts. Two points make the apicoplast of interest as a potential drug target: 1) the human host lacks organelles related to the apicoplast, and 2) the apicoplast appears to be essential in
T. gondii and Plasmodium. The apicoplast is bounded by four membranes, suggesting it arose from a secondary endosymbiosis in which the apicomplexan ancestor engulfed a photosynthetic alga. Most apicoplast
proteins appear to be encoded in the nucleus. To
dissect the
epitope or GFP-tagged versions of
proteins destined for the apicoplast. Early in
this project, our studies, as well as those of
others, demonstrated that proteins that reside
in the apicoplast lumen contain a bipartite
N-terminal targeting sequence that routes them
first into the ER and from there to the
apicoplast. More recently, we have focused on
membrane proteins, identifying the first
apicoplast membrane proteins in T. gondii.
These proteins lack the canonical targeting
sequences typical of lumenal proteins. We have
shown that the proteins traffic in vesicles and
that this trafficking occurs primarily during
the stage of the cell cycle when the apicoplast
is enlarging prior to division. Future studies
are aimed at dissecting the sequences and
mechanisms responsible for routing membrane
proteins to the apicoplast.
This work is a collaboration with the Feagin lab at SBRI,
the Coppens lab at Johns Hopkins University, and the Bradley lab at UCLA.
It has been funded by a grant from the National Institutes of Health: R01 AI
50506 Marilyn Parsons, Principal Investigator.
This immunofluorescence image shows a host cell infected
with multiple T. gondii parasites. Distribution of Toxoplasma
apicoplast phosphate translocator APT1 (green) varies during the cell cycle as
revealed by plastid shape and location (red), inner membrane complex formation
(magenta) and nuclear position (blue). The large blue object is the host cell
nucleus. (Karnataki et al., PMID: 17367386.
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