Assembling the components of the quorum sensing pathway in African trypanosomes.
Bottom Line: These resemble components of nutritional starvation and quiescence pathways in other eukaryotes, suggesting that parasite development shares similarities with the adaptive quiescence of organisms such as yeasts and Dictyostelium in response to nutritional starvation and stress.Here, the trypanosome signalling pathway is discussed in the context of these conserved pathways and the possible contributions of opposing 'slender retainer' and 'stumpy inducer' arms described.As evolutionarily highly divergent eukaryotes, the organisation and conservation of this developmental pathway can provide insight into the developmental cycle of other protozoan parasites, as well as the adaptive and programmed developmental responses of all eukaryotic cells.
Affiliation: Centre for Immunity, Infection and Evolution, Institute for Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Charlotte Auerbach Road, Edinburgh, EH9 3FL, UK.Show MeSH
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Mentions: This ability of monomorphs to respond to 8-pCPT-cAMP/AMP and undergo growth arrest has been exploited in a genome-wide RNAi library screen that sought to select parasites that were unresponsive to 8-pCPT-cAMP/AMP after gene knockdown. The monomorphic library, capable of tetracycline-induced gene silencing on a genome-wide scale, was exposed to 8-pCPT-cAMP/AMP, following which, growth was monitored and compared with the uninduced set. The parasites that failed to undergo growth arrest were believed to continue proliferation due to the knockdown of a gene required for sensing the 8-pCPT-cAMP/AMP signal. Deep sequencing of the RNAi inserts enriched in the selected 8-pCPT-cAMP/AMP resistant parasite population divulged a collection of genes representing various steps of a typical signalling pathway and likely to be involved in the 8-pCPT-cAMP/AMP response (Fig. 2). Crucially, when many of these genes were individually knocked down in pleomorphs by RNAi, they conferred resistance to SIF in vivo thereby confirming their involvement in the biologically relevant QS signalling pathway. This demonstrated that the 8-pCPT-cAMP/AMP–mediated pathway intersected with the SIF signalling pathway at least to some extent, though inevitably molecules involved in the reception of the SIF signal were missing given the use of a cell permeable signal in the screen (Mony et al., 2013).
Affiliation: Centre for Immunity, Infection and Evolution, Institute for Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Charlotte Auerbach Road, Edinburgh, EH9 3FL, UK.