title: An actin cytoskeleton with evolutionarily conserved functions in the absence of canonical actin-binding proteins.
abstract: 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.
authors: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
authors: Alexander R
authors: AR
authors: Paredez
authors: Zoe June
authors: ZJ
authors: Assaf
authors: David
authors: D
authors: Sept
authors: Ljudmilla
authors: L
authors: Timofejeva
authors: Scott C
authors: SC
authors: Dawson
authors: Chung-Ju Rachel
authors: CJ
authors: Wang
authors: W Z
authors: WZ
authors: Cande
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003560:Cysts / Q000382:microbiology; D003599:Cytoskeleton / Q000378:metabolism*; D019143:Evolution, Molecular; D055785:Gene Knockdown Techniques; D016829:Giardia lamblia / Q000378:metabolism* / Q000472:pathogenicity; D005873:Giardiasis / Q000382:microbiology*; D006801:Humans; D007422:Intestines / Q000382:microbiology; D008840:Microfilament Proteins / Q000378:metabolism*; D011817:Rabbits
chemical_list: D000199:Actins; D008840:Microfilament Proteins