Giardia spp.: Distribution of contractile proteins in the attachment organelle

Feely, Dennis E.; Schollmeyer, Judy V.; Erlandsen, Stanley L.

doi:10.1016/0014-4894(82)90100-x

Cited by 87 publications

(67 citation statements)

References 22 publications

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“…S2). We observed filamentous actin structures within Giardia, and in contrast to previous studies using heterologous antibodies of unknown specificity (19,20), we did not observe pronounced actin staining of the ventral disk, a microtubule structure used for parasite attachment.…”

Section: Resultscontrasting

confidence: 99%

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

Paredez

Assaf

Sept

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

166

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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. cytoskeleton evolution | actin protofilaments | MreB | endocytosis | Rac

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Section: Resultscontrasting

confidence: 99%

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

Paredez

Assaf

Sept

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

166

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“…This suggests a difference between the tubulin found in the ventral disk and that found in the flagella. This, as well as the observation that adherence can occur in the absence of flagellar function (103), suggest that the ventral disk is important for adherence but the flagella are not. With more prolonged exposure (e.g.…”

Section: Cytoskeleton and Motilitymentioning

confidence: 82%

Biology ofGiardia lamblia

2001

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Giardia lamblia is a common cause of diarrhea in humans and other mammals throughout the world. It can be distinguished from other Giardia species by light or electron microscopy. The two major genotypes of G. lamblia that infect humans are so different genetically and biologically that they may warrant separate species or subspecies designations. Trophozoites have nuclei and a well-developed cytoskeleton but lack mitochondria, peroxisomes, and the components of oxidative phosphorylation. They have an endomembrane system with at least some characteristics of the Golgi complex and encoplasmic reticulum, which becomes more extensive in encysting organisms. The primitive nature of the organelles and metabolism, as well as small-subunit rRNA phylogeny, has led to the proposal that Giardia spp. are among the most primitive eukaryotes. G. lamblia probably has a ploidy of 4 and a genome size of approximately 10 to 12 Mb divided among five chromosomes. Most genes have short 5′ and 3′ untranslated regions and promoter regions that are near the initiation codon. Trophozoites exhibit antigenic variation of an extensive repertoire of cysteine-rich variant-specific surface proteins. Expression is allele specific, and changes in expression from one vsp gene to another have not been associated with sequence alterations or gene rearrangements. The Giardia genome project promises to greatly increase our understanding of this interesting and enigmatic organism

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“…5C), no cyst with anti-FLAG staining was found, in accordance with the observed difficulty of this transgenic line to form cysts. In the trophozoite stage, anti-FLAG markedly stained the cell ventral surface, nearly corresponding to specialized contractile structures with a role in G. duodenalis attachment and termed marginal groove and ventrolateral flanges (31)(32)(33). A diffuse anti-FLAG staining was also present in the nuclei and in the median body (Fig.…”

Section: Intracellular Localization Of Flag-gttll3 and Flaggdips And mentioning

confidence: 87%

Giardia Duodenalis 14-3-3 Protein Is Polyglycylated by a Tubulin Tyrosine Ligase-like Member and Deglycylated by Two Metallocarboxypeptidases

Lalle¹,

Camerini

Cecchetti

et al. 2011

Journal of Biological Chemistry

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The flagellated protozoan Giardia duodenalis is a parasite of the upper part of the small intestine of mammals, including humans, and an interesting biological model. Giardia harbors a single 14-3-3 isoform, a multifunctional protein family, that is modified at the C terminus by polyglycylation, an unusual post-translational modification consisting of the covalent addition of one or multiple glycines on the ␥-carboxyl groups of specific glutamic acids. Polyglycylation affects the intracellular localization of g14-3-3, as the shortening of the polyglycine chain is correlated with a partial relocalization of 14-3-3 inside the nuclei during encystation. In this work we demonstrate that the gTTLL3, a member of the tubulin tyrosine ligase-like family, is the enzyme responsible for the 14-3-3 polyglycylation. We also identify two metallopeptidases of the M20 family, here termed gDIP1 (giardial dipeptidase 1) and gDIP2, as enzymes able to shorten the g14-3-3 polyglycine tail both in vivo and in vitro. Finally, we show that the ectopic expression of gDIP2 alters the g14-3-3 localization and strongly hampers the cyst formation. In conclusion, we have identified a polyglycylase and two deglycylases that act in concert to modulate the stage-dependent glycylation status of the multifunctional regulatory g14-3-3 protein in G. duodenalis. The flagellated and binucleated protozoan Giardia duodenalis (synonymous of Giardia lamblia and Giardia intestinalis)is an extracellular parasite of the upper part of the small intestine of mammals, including humans, where it causes giardiasis, an acute enteritis (1). Besides its relevance for human and animal health, G. duodenalis is also a fascinating and simple eukaryotic organism with a minimalistic genomic and cellular organization that arouses a great interest as a biological model (2). In this perspective we have previously characterized the single giardial 14-3-3 (g14-3-3) isoform, a member of a small dimeric protein family ubiquitously conserved in eukaryotes (3, 4). The 14-3-3s are able to bind a wide range of proteins containing consensus binding motifs usually phosphorylated on serine or threonine, thus, regulating multiple cellular processes, i.e. the metabolism, cell cycle progression, signal transduction pathways, cell growth, and differentiation (5). We demonstrated that the g14-3-3 is modified in a peculiar fashion by the phosphorylation of Thr-214 and the polyglycylation of 4). The glycylation, first discovered at the C-terminal domain of ␣-and ␤-tubulin, is a post-translational modification consisting of the covalent addition of one or multiple glycines to the ␥-carboxyl groups of specific glutamic acids of target proteins (6, 7). Recently, polyglycylation has been also reported for several proteins, including the mammalian nucleosome assembly proteins (8 -10). Whereas the phosphorylation of g14-3-3 is a constitutive post-translational modification, the polyglycylation of the protein is regulated during the G. duodenalis life cycle with a remarkable reduction in the length...

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Giardia spp.: Distribution of contractile proteins in the attachment organelle

Cited by 87 publications

References 22 publications

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

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

Biology ofGiardia lamblia

Giardia Duodenalis 14-3-3 Protein Is Polyglycylated by a Tubulin Tyrosine Ligase-like Member and Deglycylated by Two Metallocarboxypeptidases

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