The complex life cycle of Trypanosoma brucei provides an excellent model system to understand signalling pathways that regulate development. We described previously the classical functions of TOR (target of rapamycin) 1 and TOR2 in T. brucei. In a more recent study, we described a novel TOR kinase, named TOR4, which regulates differentiation from the proliferative infective form to the quiescent form. In contrast with TOR1 loss-of-function, down-regulation of TOR4 triggers an irreversible differentiation process through the development of the insect pre-adapted quiescent form. TOR4 governs a signalling pathway distinct from those controlled by the conventional TOR complexes TORC1 and TORC2. Depletion of TOR4 induces all well-known characteristics of the quiescent developmental stage in trypanosomes, including expression of the PAD (proteins associated with differentiation) surface proteins and transcriptional down-regulation of the VSG (variant surface glycoprotein) gene. TOR4 kinase forms a structurally and functionally distinct complex named TORC4. TOR4 associates with LST8 (lethal with sec-13 protein 8) and other factors including an armadillo-domain-containing protein and the major vault protein, which probably serves as a scaffold for this kinase. Research in T. brucei, a protozoan parasite that diverged from the eukaryotic tree early in evolution, may help to uncover new functions of TOR kinases.
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August 2013
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Conference Article|
July 18 2013
Target of rapamycin (TOR) kinase in Trypanosoma brucei: an extended family
Manuel Saldivia;
Manuel Saldivia
*Consejo Superior de Investigaciones Cientificas, IPBLN, 18100 Granada, Spain
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Antonio Barquilla;
Antonio Barquilla
*Consejo Superior de Investigaciones Cientificas, IPBLN, 18100 Granada, Spain
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Jean-Mathieu Bart;
Jean-Mathieu Bart
*Consejo Superior de Investigaciones Cientificas, IPBLN, 18100 Granada, Spain
†Centro Nacional de Medicina Tropical, ISCIII, 28019 Madrid, Spain
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Rosario Diaz-González;
Rosario Diaz-González
*Consejo Superior de Investigaciones Cientificas, IPBLN, 18100 Granada, Spain
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Michael N. Hall;
Michael N. Hall
‡Biozentrum, University of Basel, CH-4056 Basel, Switzerland
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Miguel Navarro
Miguel Navarro
1
*Consejo Superior de Investigaciones Cientificas, IPBLN, 18100 Granada, Spain
1To whom correspondence should be addressed (emailmiguel.navarro@ipb.csic.es).
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Biochem Soc Trans (2013) 41 (4): 934–938.
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Received:
April 11 2013
Citation
Manuel Saldivia, Antonio Barquilla, Jean-Mathieu Bart, Rosario Diaz-González, Michael N. Hall, Miguel Navarro; Target of rapamycin (TOR) kinase in Trypanosoma brucei: an extended family. Biochem Soc Trans 1 August 2013; 41 (4): 934–938. doi: https://doi.org/10.1042/BST20130052
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