Third target of rapamycin complex negatively regulates development of quiescence in Trypanosoma brucei
| Autor: | Rosario Diaz, Manuel Saldivia, Miguel Navarro, Jean-Mathieu Bart, Enrique Calvo, Isabel Vidal, Antonio Barquilla, Michael N. Hall |
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| Rok vydání: | 2012 |
| Předmět: |
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Western Trypanosoma brucei brucei Trypanosoma brucei 03 medical and health sciences Major vault protein Cyclic AMP TOR complex Immunoprecipitation 030304 developmental biology Vault Ribonucleoprotein Particles Regulation of gene expression 0303 health sciences Multidisciplinary biology Kinase TOR Serine-Threonine Kinases 030302 biochemistry & molecular biology Biological Sciences biology.organism_classification Adaptation Physiological Adenosine Monophosphate 3. Good health Cell biology TOR signaling Biochemistry Gene Expression Regulation Microscopy Fluorescence Multiprotein Complexes biology.protein Signal transduction Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 1091-6490 |
| Popis: | African trypanosomes are protozoan parasites transmitted by a tsetse fly vector to a mammalian host. The life cycle includes highly proliferative forms and quiescent forms, the latter being adapted to host transmission. The signaling pathways controlling the developmental switch between the two forms remain unknown. Trypanosoma brucei contains two target of rapamycin (TOR) kinases, TbTOR1 and TbTOR2, and two TOR complexes, TbTORC1 and TbTORC2. Surprisingly, two additional TOR kinases are encoded in the T. brucei genome. We report that TbTOR4 associates with an Armadillo domain-containing protein (TbArmtor), a major vault protein, and LST8 to form a unique TOR complex, TbTORC4. Depletion of TbTOR4 caused irreversible differentiation of the parasite into the quiescent form. AMP and hydrolysable analogs of cAMP inhibited TbTOR4 expression and induced the stumpy quiescent form. Our results reveal unexpected complexity in TOR signaling and show that TbTORC4 negatively regulates differentiation of the proliferative form into the quiescent form. |
| Databáze: | OpenAIRE |
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