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An actin cytoskeleton with evolutionarily conserved functions in the absence of canonical actin-binding proteins.

TitleAn actin cytoskeleton with evolutionarily conserved functions in the absence of canonical actin-binding proteins.
Publication TypeJournal Article
Year of Publication2011
AuthorsParedez AR, Assaf Z J, Sept D, Timofejeva L, Dawson SC, Wang C-J R, Cande WZ
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue15
Pagination6151-6
Date Published2011 Apr 12
ISSN1091-6490
KeywordsActins, Animals, Cercopithecus aethiops, COS Cells, Cysts, cytoskeleton, Evolution, Molecular, Gene Knockdown Techniques, Giardia lamblia, Giardiasis, Humans, Intestines, Microfilament Proteins, Rabbits
Abstract

<p>Giardia intestinalis, a human intestinal parasite and member of what is perhaps the earliest-diverging eukaryotic lineage, contains the most divergent eukaryotic actin identified to date and is the first eukaryote known to lack all canonical actin-binding proteins (ABPs). We sought to investigate the properties and functions of the actin cytoskeleton in Giardia to determine whether Giardia actin (giActin) has reduced or conserved roles in core cellular processes. In vitro polymerization of giActin produced filaments, indicating that this divergent actin is a true filament-forming actin. We generated an anti-giActin antibody to localize giActin throughout the cell cycle. GiActin localized to the cortex, nuclei, internal axonemes, and formed C-shaped filaments along the anterior of the cell and a flagella-bundling helix. These structures were regulated with the cell cycle and in encysting cells giActin was recruited to the Golgi-like cyst wall processing vesicles. Knockdown of giActin demonstrated that giActin functions in cell morphogenesis, membrane trafficking, and cytokinesis. Additionally, Giardia contains a single G protein, giRac, which affects the Giardia actin cytoskeleton independently of known target ABPs. These results imply that there exist ancestral and perhaps conserved roles for actin in core cellular processes that are independent of canonical ABPs. Of medical significance, the divergent giActin cytoskeleton is essential and commonly used actin-disrupting drugs do not depolymerize giActin structures. Therefore, the giActin cytoskeleton is a promising drug target for treating giardiasis, as we predict drugs that interfere with the Giardia actin cytoskeleton will not affect the mammalian host.</p>

DOI10.1073/pnas.1018593108
Alternate JournalProc. Natl. Acad. Sci. U.S.A.