Right place, right time: Environmental sensing and signal transduction directs cellular differentiation and motility in Trypanosoma brucei

2021 ◽  
Author(s):  
Breanna Walsh ◽  
Kent L. Hill
1995 ◽  
Vol 350 (1331) ◽  
pp. 59-65 ◽  

All metazoan cells are able to make decisions about cell division or cellular differentiation based, in part, on environmental cues. Accordingly, cells express receptor systems that allow them to detect the presence of hormones, growth factors and other signals that manipulate the regulatory processes of the cell. In plants, an unusual signal - light - is required for the induction and regulation of many developmental processes. Past physiological and molecular studies have revealed the variety and complexity of plant responses to light but until recently very little was known about the mechanisms of those responses. Two major breakthroughs have allowed the identification of some photoreceptor signalling intermediates: the identification of photoreceptor and signal transduction mutants in Arabidopsis , and the development of single-cell microinjection assays in which outcomes of photoreceptor signalling can be visualized. Here, we review recent genetic advances which support the notion that light responses are not simply endpoints of linear signal transduction pathways, but are the result of the integration of a variety of input signals through a complex network of interacting signalling components.


2020 ◽  
Author(s):  
Eva Horáková ◽  
Laurence Lecordier ◽  
Paula Cunha ◽  
Roman Sobotka ◽  
Piya Changmai ◽  
...  

Abstract Resistance to African trypanosomes in humans relies on targeting of a trypanosome lytic factor 1 (TLF1) to trypanosome haptoglobin-hemoglobin receptor (HpHbR). While TLF1 avoidance by the inactivation of the HpHbR contributes to Trypanosoma brucei gambiense human infectivity, the evolutionary trade-off of this adaptation is unknown. Both T. b. gambiense with inactive HpHbR, as well as a genetically engineered T.b.brucei HpHbR knock-out show only trace levels of intracellular heme and lack the downstream hemoprotein activities, thereby providing an extraordinary example of aerobic parasite proliferation in the absence of heme. We further show that HpHbR facilitates the developmental progression by inducing PAD-1 expression that is associated with the formation of cell cycle-arrested stumpy forms in T. b.brucei . Accordingly, T. b. gambiense was found to be poorly competent for slender-to-stumpy differentiation unless a functional HpHbR receptor derived from T. b. brucei was genetically restored.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Mathieu Cayla ◽  
Lindsay McDonald ◽  
Paula MacGregor ◽  
Keith Matthews

The sleeping sickness parasite, Trypanosoma brucei, uses quorum sensing (QS) to balance proliferation and transmission potential in the mammal bloodstream. A signal transduction cascade regulates this process, a component of which is a divergent member of the DYRK family of protein kinases, TbDYRK. Phylogenetic and mutational analysis in combination with activity and phenotypic assays revealed that TbDYRK exhibits a pre-activated conformation and an atypical HxY activation loop motif, unlike DYRK kinases in other eukaryotes. Phosphoproteomic comparison of TbDYRK null mutants with wild-type parasites identified molecules that operate on both the inhibitory ‘slender retainer’ and activatory ‘stumpy inducer’ arms of the QS control pathway. One of these molecules, the RNA-regulator TbZC3H20, regulates parasite QS, this being dependent on the integrity of its TbDYRK phosphorylation site. This analysis reveals fundamental differences to conventional DYRK family regulation and links trypanosome environmental sensing, signal transduction and developmental gene expression in a coherent pathway.


2019 ◽  
Author(s):  
Mathieu Cayla ◽  
Lindsay McDonald ◽  
Paula MacGregor ◽  
Keith R. Matthews

AbstractThe sleeping sickness parasite, Trypanosoma brucei, uses quorum sensing (QS) to balance proliferation and transmission potential in the mammal bloodstream. A signal transduction cascade regulates this process, a component of which is a divergent member of the DYRK family of protein kinases, TbDYRK. Phylogenetic and mutational analysis in combination with activity and phenotypic assays revealed that TbDYRK exhibits a pre-activated confirmation and an atypical HxY activation loop motif, unlike DYRK kinases in other eukaryotes. Phosphoproteomic comparison of TbDYRK null mutants with wild type parasites identified molecules that operate on both the inhibitory ‘slender retainer’ and activatory ‘stumpy inducer’ arms of the QS control pathway. One of these molecules, the RNA-regulator TbZC3H20, regulates parasite QS, this being dependent on the integrity of its TbDYRK phosphorylation site. This analysis reveals fundamental differences to conventional DYRK family regulation and links trypanosome environmental sensing, signal transduction and developmental gene expression in a coherent pathway.


Author(s):  
Bert Ph. M. Menco

Vertebrate olfactory receptor cells are specialized neurons that have numerous long tapering cilia. The distal parts of these cilia line the interface between the external odorous environment and the luminal surface of the olfactory epithelium. The length and number of these cilia results in a large surface area that presumably increases the chance that an odor molecule will meet a receptor cell. Advanced methods of cryoprepration and immuno-gold labeling were particularly useful to preserve the delicate ultrastructural and immunocytochemical features of olfactory cilia required for localization of molecules involved in olfactory signal-transduction. We subjected olfactory tissues to freeze-substitution in acetone (unfixed tissues) or methanol (fixed tissues) followed by low temperature embedding in Lowicryl K11M for that purpose. Tissue sections were immunoreacted with several antibodies against proteins that are presumably important in olfactory signal-transduction.


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