cAMP signalling in Trypanosoma brucei

Seebeck, Thomas; Gong, KewWei; Kunz, Stefan; Schaub, Rahel; Shalaby, Tarek; Zoraghi, Roya

doi:10.1016/s0020-7519(01)00164-3

Cited by 44 publications

(27 citation statements)

References 35 publications

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“…However, no direct role or requirement for cAMP in these processes has been demonstrated. Moreover, older studies in trypanosomes assumed that modulators of mammalian cyclases or PDEs also were effective on their counterparts in trypanosomes (14, 15,38). We now know that most of these pharmacological agents do not affect trypanosome PDEs or cyclases.…”

Section: Discussionmentioning

confidence: 99%

Hydrolysis products of cAMP analogs cause transformation ofTrypanosoma bruceifrom slender to stumpy-like forms

Laxman¹,

Riechers²,

Sadı́lek

et al. 2006

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

110

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African sleeping sickness is a disease caused by Trypanosoma brucei. T. brucei proliferate rapidly in the mammalian bloodstream as long, slender forms, but at higher population densities they transform into nondividing, short, stumpy forms. This is thought to be a mechanism adopted by T. brucei to establish a stable hostparasite relationship and to allow a transition into the insect stage of its life cycle. Earlier studies have suggested a role for cAMP in mediating this transformation. In this study, using membranepermeable nucleotide analogs, we show that it is not the cAMP analogs themselves but rather the hydrolyzed products of membrane-permeable cAMP analogs that prevent proliferation of T. brucei. The metabolic products are more potent than the cAMP analogs, and hydrolysis-resistant cAMP analogs are not antiproliferative. We further show that the antiproliferative effect of these membrane-permeable adenosine analogs is caused by transformation into forms resembling short, stumpy bloodstream forms. These data suggest that the slender-to-stumpy transformation of T. brucei may not be mediated directly by cAMP and also raise the possibility of using such adenosine analogs as antitrypanosomal drugs.adenosine ͉ EPACs ͉ phosphodiesterases ͉ trypanosomes

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Section: Discussionmentioning

confidence: 99%

Hydrolysis products of cAMP analogs cause transformation ofTrypanosoma bruceifrom slender to stumpy-like forms

Laxman¹,

Riechers²,

Sadı́lek

et al. 2006

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

110

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show abstract

“…In addition, the leucinerich repeat region of PF6-IP1 aligns with the CAP_ED domain of the Trypanosoma predicted regulatory subunit (29% identity, 51% similarity). The CAP_ED domain (CD00038) (Marchler-Bauer et al, 2005) is a conserved set of amino acids that binds cyclic nucleotides or assists in the binding of flavin groups; the predicted trypanosome CAP_ED-containing protein has been shown to stimulate the PKA catalytic subunit in a cAMP-dependent manner (Seebeck et al, 2001). The similarity of PF6-IP1 and the trypanosome CAP_ED suggests that PF6-IP1 may function as an unconventional regulatory subunit.…”

Section: Discussionmentioning

confidence: 99%

Calmodulin and PF6 are components of a complex that localizes to the C1 microtubule of the flagellar central apparatus

Wargo

Dymek

Smith

2005

Journal of Cell Science

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“…Since cAMP is a small molecule with a high diffusion coefficient, and trypanosomes have a length of 20µm and a diameter of only 2µm, it would rapidly equilibrate throughout the cell unless there was a stringent system of control [41].…”

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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cAMP signalling in Trypanosoma brucei

Cited by 44 publications

References 35 publications

Hydrolysis products of cAMP analogs cause transformation ofTrypanosoma bruceifrom slender to stumpy-like forms

Hydrolysis products of cAMP analogs cause transformation ofTrypanosoma bruceifrom slender to stumpy-like forms

Calmodulin and PF6 are components of a complex that localizes to the C1 microtubule of the flagellar central apparatus

The Social Life of African Trypanosomes

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