Spontaneous dimerization and leucine-zipper induced activation of the recombinant catalytic domain of a new adenylyl cyclase of Trypanosoma brucei, GRESAG4.4B

Naula, Christina; Schaub, Rahel; Leech, Vanessa; Melville, Sara E.; Seebeck, Thomas

doi:10.1016/s0166-6851(00)00338-8

Cited by 37 publications

(29 citation statements)

References 34 publications

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“…These adenylate cyclases are part of a previously described family of genes related to expression site-associated gene 4 (GRESAG4), on the basis of their sequence similarity to ESAG4 (23). ESAG4 is expressed only in BSF parasites, while previously examined GRESAG4 genes were found to be constitutively expressed in both BSF and PCF parasites (18,23,29,33,34). We were therefore surprised to uncover a group of GRESAG4 genes that were detected only in procyclic flagella, and we investigated these further.…”

Section: Resultsmentioning

confidence: 97%

“…1A). In vitro studies with recombinant catalytic domains previously demonstrated that T. brucei AC catalytic domains require dimerization for catalytic ac- tivity (34,59), but whether the full-length proteins form dimers in vivo is not known. We therefore asked whether native T. brucei ACs formed multimeric complexes by examining cell lysates using Blue Native gels under nonreducing conditions.…”

Section: Resultsmentioning

confidence: 99%

“…Trypanosomal adenylate cyclases exhibit sequence diversity in their extracellular domains, which suggests a mechanism for ligand-specific regulation of AC activity (24,32), making these proteins well-suited for directing cAMP signaling in response to host-specific signals. To date, however, all GRESAG4 genes studied have been found to be expressed in both bloodstream-stage and insect-stage cells (18,23,29,33,34), raising questions about whether they are responsible for procyclic stage-specific regulation of cAMP production. Here we report on the identification of a group of T. brucei adenylate cyclases whose expression is upregulated in procyclic cells.…”

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confidence: 99%

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Insect Stage-Specific Receptor Adenylate Cyclases Are Localized to Distinct Subdomains of the Trypanosoma brucei Flagellar Membrane

et al. 2014

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cIncreasing evidence indicates that the Trypanosoma brucei flagellum (synonymous with cilium) plays important roles in hostparasite interactions. Several studies have identified virulence factors and signaling proteins in the flagellar membrane of bloodstream-stage T. brucei, but less is known about flagellar membrane proteins in procyclic, insect-stage parasites. Here we report on the identification of several receptor-type flagellar adenylate cyclases (ACs) that are specifically upregulated in procyclic T. brucei parasites. Identification of insect stage-specific ACs is novel, as previously studied ACs were constitutively expressed or confined to bloodstream-stage parasites. We show that procyclic stage-specific ACs are glycosylated, surface-exposed proteins that dimerize and possess catalytic activity. We used gene-specific tags to examine the distribution of individual AC isoforms. All ACs examined localized to the flagellum. Notably, however, while some ACs were distributed along the length of the flagellum, others specifically localized to the flagellum tip. These are the first transmembrane domain proteins to be localized specifically at the flagellum tip in T. brucei, emphasizing that the flagellum membrane is organized into specific subdomains. Deletion analysis reveals that C-terminal sequences are critical for targeting ACs to the flagellum, and sequence comparisons suggest that differential subflagellar localization might be specified by isoform-specific C termini. Our combined results suggest insect stage-specific roles for a subset of flagellar adenylate cyclases and support a microdomain model for flagellar cyclic AMP (cAMP) signaling in T. brucei. In this model, cAMP production is compartmentalized through differential localization of individual ACs, thereby allowing diverse cellular responses to be controlled by a common signaling molecule.

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Insect Stage-Specific Receptor Adenylate Cyclases Are Localized to Distinct Subdomains of the Trypanosoma brucei Flagellar Membrane

et al. 2014

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“…Trypanosomal ACs have the capacity to dimerise [37,39], but it is not yet known if AC1 and AC6 are part of a single complex that operates as a functional unit. In this context, other ACs that are stage-regulated between early and late procyclic forms also merit further investigation.…”

Section: Somo Is Regulated By Adenylyl Cyclases and A Phosphodiesterasementioning

confidence: 99%

The Social Life of African Trypanosomes

Imhof

Roditi

2015

Trends in Parasitology

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The unicellular parasite Trypanosoma brucei shuttles between its definitive host, the tsetse fly, and various mammals including humans. In the fly T. brucei must first migrate to the ectoperitrophic space, establish a persistent infection of the midgut and then migrate to the salivary glands before being transmitted to a new mammalian host. In 2010 it was shown that insect stages of the parasite (procyclic forms) exhibit social motility (SoMo) when cultured on a semi-solid surface, and it was postulated that this behaviour might reflect a migration step in the tsetse fly. Now, almost five years after the initial report, several new publications shed some light on the biological function of SoMo and provide insights into the underlying signaling pathways.

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“…Other adenylate cyclases are differentially regulated between early and late procyclic forms, but it is not known if they play a role in SoMo [16]. All trypanosomal adenylate cyclases have a large extracellular domain, a single trans-membrane domain and an intracellular catalytic domain [23]. No ligands that regulate their activities have been identified.…”

Section: Coordinated Group Movement -The Phenomenon Of Social Motilitymentioning

confidence: 99%

The languages of parasite communication

Roditi

2016

Molecular and Biochemical Parasitology

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Although it is regarded as self-evident that parasites interact with their hosts, with the primary aim of enhancing their own survival and transmission, the extent to which unicellular parasites communicate with each has been severely underestimated.Recent publications show that information is commonly exchanged between parasites of the same species and that this can govern their decisions to divide, to differentiate or to migrate as a group. Communication can take the form of soluble secreted factors, extracellular vesicles or contact between cells. Extracellular parasites can do this directly, while intracellular parasites use the infected host cell -or components derived from it -as an intermediary. By emitting signals that can be dispersed within the host, parasites can also have long-distance effects on the course of an infection and its pathology. This article presents an overview of recent developments in this field and draws attention to some older work that merits re-examination. 3 Most readers of this article will not need to be told that diseases such as sleeping sickness, malaria, Leishmaniasis, Trichomoniasis and Chagas Disease are caused by unicellular parasites. This knowledge might come with the tacit assumption that singlecelled organisms are completely self-sufficient and have no need to interact, much less cooperate, with members of their own species. In recent years, however, it has become apparent that a number of decisions are group decisions that rely on parasites communicating with each other. Just as animals can exchange information in different ways, be it vocally, visually, chemically or by body language, parasites have also developed a range of mechanisms for communicating with each other. This sometimes occurs directly, from parasite to parasite, or by using the infected host cell -or components derived from it -as an intermediary. By emitting signals that can be dispersed within the host, parasites can also have wide-ranging effects on the course of an infection and its pathology. This article presents an overview of recent developments in this field and draws attention to some older work that merits re-examination. Owing to space constraints, it will not cover molecules used by intracellular parasites to reprogram the cells that they infect. Quorum sensing and differentiationDifferent subspecies of Trypanosoma brucei, the pathogens responsible for human sleeping sickness and Nagana in domestic animals, are extracellular throughout their life cycle. In the mammalian host the parasites use a quorum sensing mechanism to maintain a balance between slender bloodstream forms, which are capable of dividing every 6-8 hours, and stumpy bloodstream forms, which cannot divide and have a lifespan of a few days. When trypanosomes ingested by a tsetse fly, the slender form is killed while the stumpy form survives and differentiates to the next life stage, the procyclic form, in the insect midgut [1,2]. If slender forms were to proliferate unchecked, this would result in rapid death of th...

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Spontaneous dimerization and leucine-zipper induced activation of the recombinant catalytic domain of a new adenylyl cyclase of Trypanosoma brucei, GRESAG4.4B

Cited by 37 publications

References 34 publications

Insect Stage-Specific Receptor Adenylate Cyclases Are Localized to Distinct Subdomains of the Trypanosoma brucei Flagellar Membrane

Insect Stage-Specific Receptor Adenylate Cyclases Are Localized to Distinct Subdomains of the Trypanosoma brucei Flagellar Membrane

The Social Life of African Trypanosomes

The languages of parasite communication

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