Calcium Signaling in Excystation of the Early Diverging Eukaryote, Giardia lamblia

Reiner, David S.; Hetsko, Michael L.; Meszaros, J. Gary; Sun, Chin-Hung; Morrison, Hilary G.; Brunton, Laurence L.; Gillin, Frances D.

doi:10.1074/jbc.m208033200

Cited by 33 publications

(22 citation statements)

References 61 publications

(79 reference statements)

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“…In Giardia trophozoites, gPP2A-C localizes to the eight basal bodies, as previously reported for giardial PKAc/r, the MAP kinase ERK1, centrin, and calmodulin [7][8][9]24,38,39]. gPP2A-C also localizes to the ventral disk (similar to ERK 1 [9]), to the anterior and caudal PDR (similar to PKAc/r [7,8]) and to the posterior-lateral PDR (similar to centrin [24]).…”

Section: Discussionsupporting

confidence: 81%

Protein phosphatase 2A plays a crucial role in Giardia lamblia differentiation

Lauwaet

Davids

Torres-Escobar

et al. 2007

Molecular and Biochemical Parasitology

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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.

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Section: Discussionsupporting

confidence: 81%

Protein phosphatase 2A plays a crucial role in Giardia lamblia differentiation

Lauwaet

Davids

Torres-Escobar

et al. 2007

Molecular and Biochemical Parasitology

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“…Bernal et al (1998) evaluated the effect of CaM inhibitors and found that excystation (shift from cyst to trophozoite) decreased in the presence of TFP and W-7 compounds. Reiner et al (2003) repeated these inhibition experiments and confirmed that CaM was involved in parasite excystation. They also sequenced the CaM gene and found, by analyzing the translated sequence, that the protein was divergent and differed from the consensus of all available sequences in ten positions (Reiner et al 2003).…”

Section: Introductionsupporting

confidence: 70%

“…Reiner et al (2003) repeated these inhibition experiments and confirmed that CaM was involved in parasite excystation. They also sequenced the CaM gene and found, by analyzing the translated sequence, that the protein was divergent and differed from the consensus of all available sequences in ten positions (Reiner et al 2003). This is very interesting because CaM has been one of the most conserved proteins during evolution (Stathopulos et al 2007).…”

Section: Introductionsupporting

confidence: 70%

“…The protein's localization was determined; the immunofluorescence results showed that CaM is an abundant protein that becomes concentrated in key locomotion structures such as the basal bodies and axonemes. Reiner et al (2003), transformed G. intestinalis trophozoites with the CaM gene fusioned to an AU1 tag and localized the protein by using this tag. They reported localization in the basal bodies and a variable quantity of CaM in the cytoplasm.…”

Section: Discussionmentioning

confidence: 99%

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Calmodulin expression during Giardia intestinalis differentiation and identification of calmodulin-binding proteins during the trophozoite stage

Alvarado

Wasserman

2011

Parasitol Res

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Calmodulin (CaM) is the primary sensor for calcium in the cell. It modulates various functions by activating CaM-binding proteins (CaMBPs). This study examined the calcium/CaM-dependent system in the ancient eukaryote Giardia intestinalis. A specific antibody against the parasite's CaM was developed; this protein's expression and location during different stages of the parasite's life cycle were analyzed. The results showed that it is a housekeeping protein which is possibly involved in the parasite's motility. No CaMBP has been identified in G. intestinalis to date. Pull-down assays were used for isolating proteins which specifically bind to CaM in a calcium-dependent way. Three of them were identified through mass spectrometry; they were GASP180, α-tubulin, and pyruvate phosphate dikinase (PPDK).The first two are cytoskeleton proteins, and the last one is an essential enzyme for glycolysis. The presence of binding sites was analyzed through bioinformatics in each protein sequence. This is the first report of a CaMBP in this organism; it is considered to be a very interesting differentiation model, indicating that CaM is involved at least in two vital processes: G. intestinalis motility and energetic metabolism.

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“…Once ingested, the cyst becomes metabolically active, and excystation occurs within as little as 15 min (52). Excystation is dependent upon the gastric acid of the host stomach, cysteine proteases produced by G. duodenalis peripheral vesicles, the phosphorylation/dephosphorylation of cyst wall proteins, and Ca 2ϩ signaling (52)(53)(54)(55). The released excyzoite undergoes two rounds of binary fission while upregulating processes related to mobility and the organization of the adhesive disc (56).…”

Section: Giardiasis Life Cycle and Mechanisms Of Virulencementioning

confidence: 99%

Transmission and Epidemiology of Zoonotic Protozoal Diseases of Companion Animals

2013

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SUMMARYOver 77 million dogs and 93 million cats share our households in the United States. Multiple studies have demonstrated the importance of pets in their owners' physical and mental health. Given the large number of companion animals in the United States and the proximity and bond of these animals with their owners, understanding and preventing the diseases that these companions bring with them are of paramount importance. Zoonotic protozoal parasites, including toxoplasmosis, Chagas' disease, babesiosis, giardiasis, and leishmaniasis, can cause insidious infections, with asymptomatic animals being capable of transmitting disease.GiardiaandToxoplasma gondii, endemic to the United States, have high prevalences in companion animals.LeishmaniaandTrypanosoma cruziare found regionally within the United States. These diseases have lower prevalences but are significant sources of human disease globally and are expanding their companion animal distribution. Thankfully, healthy individuals in the United States are protected by intact immune systems and bolstered by good nutrition, sanitation, and hygiene. Immunocompromised individuals, including the growing number of obese and/or diabetic people, are at a much higher risk of developing zoonoses. Awareness of these often neglected diseases in all health communities is important for protecting pets and owners. To provide this awareness, this review is focused on zoonotic protozoal mechanisms of virulence, epidemiology, and the transmission of pathogens of consequence to pet owners in the United States.

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Calcium Signaling in Excystation of the Early Diverging Eukaryote, Giardia lamblia

Cited by 33 publications

References 61 publications

Protein phosphatase 2A plays a crucial role in Giardia lamblia differentiation

Protein phosphatase 2A plays a crucial role in Giardia lamblia differentiation

Calmodulin expression during Giardia intestinalis differentiation and identification of calmodulin-binding proteins during the trophozoite stage

Transmission and Epidemiology of Zoonotic Protozoal Diseases of Companion Animals

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