Publication Date:
2022-05-25
Description:
Author Posting. © The Authors, 2006. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Molecular and Biochemical Parasitology 152 (2007): 80-89, doi:10.1016/j.molbiopara.2006.12.001.
Description:
The ability of Giardia lamblia to undergo two distinct differentiations in
response to physiologic stimuli is central to its pathogenesis. The giardial
cytoskeleton changes drastically during encystation and excystation. However, the
signal transduction pathways mediating these transformations are poorly
understood. We tested the hypothesis that PP2A, a highly conserved
serine/threonine protein phosphatase, might be important in giardial differentiation.
We found that in vegetatively growing trophozoites, gPP2A-C protein localizes to
basal bodies/centrosomes, and to cytoskeletal structures unique to Giardia: the
ventral disk, and the dense rods of the anterior, posterior-lateral, and caudal
flagella. During encystation, gPP2A-C protein disappears from only the anterior
flagellar dense rods. During excystation, gPP2A-C localizes to the cyst wall in
excysting cysts but is not found in the wall of cysts with emerging excyzoites.
Transcriptome and immunoblot analyses indicated that gPP2A-C mRNA and
protein are upregulated in mature cysts and during the early stage of excystation
that models passage through the host stomach. Stable expression of gPP2A-C
antisense RNA did not affect vegetative growth, but strongly inhibited the
formation of encystation secretory vesicles (ESV) and water-resistant cysts.
Moreover, the few cysts that formed were highly defective in excystation.
Thus, gPP2A-C localizes to universal cytoskeletal structures and to
structures unique to Giardia. It is also important for encystation and excystation,
crucial giardial transformations that entail entry into and exit from dormancy.
Description:
This work was funded
by NIH grants GM61896, AI51687, AI42488, and DK35108. Dr. A.G. McArthur was
supported by NIH grant AI51089 and the Marine Biological Laboratory’s Program
in Global Infectious Diseases, funded by the Ellison Medical Foundation.
Keywords:
Giardia
;
Encystation
;
Excystation
;
PP2A
;
Cytoskeleton
;
Differentiation
Repository Name:
Woods Hole Open Access Server
Type:
Preprint
Format:
application/pdf
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