Leishmania dual‐specificity tyrosine‐regulated kinase 1 (DYRK1) is required for sustaining Leishmania stationary phase phenotype

Autor: Simon A. Young, Antonia Efstathiou, Milena Botelho Pereira Soares, Vinícius Pinto Costa Rocha, Mariko Dacher, Foteini Kolokousi, Despina Smirlis, Gerald F. Späth
Přispěvatelé: Instituto Gonçalo Moniz / Gonçalo Moniz Research Centre - Fiocruz Bahia [Salvador, Brésil] (IGM), Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Hospital São Rafael [Brazil], Parasitologie moléculaire et Signalisation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Centre for Biomolecular Sciences, University of St Andrews [Scotland], Institut Pasteur Hellénique, Réseau International des Instituts Pasteur (RIIP), This work was supported by the International Division of the Institute Pasteur (ACIP A13‐2013 project), the Action 'KRIPIS I' (MIS 450598) cofinanced by European Union and the National Ministry of Education and Religion Affairs under the Operational Strategic Reference Framework (NSRF 2007‐2013) and the General Secretariat of Research and Technology (GSRT) and FAPESB/CAPES grant # PET0042/2013 from the Brazilian State and Federal governments, respectively., Parasitologie moléculaire et Signalisation / Molecular Parasitology and Signaling, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), University of St Andrews. School of Biology, Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ricard Andraos, Christel
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Molecular Microbiology
Molecular Microbiology, Wiley, 2020, 113 (5), pp.983-1002. ⟨10.1111/mmi.14464⟩
Molecular Microbiology, 2020, 113 (5), pp.983-1002. ⟨10.1111/mmi.14464⟩
ISSN: 0950-382X
1365-2958
Popis: This work was supported by the International Division of the Institute Pasteur (ACIP A13-2013 project), the Action “KRIPIS I” (MIS 450598) co-financed by European Union and the National Ministry of Education and Religion Affairs under the Operational Strategic Reference Framework (NSRF 2007-2013) and the General Secretariat of Research and Technology (GSRT) and FAPESB/CAPES grant # PET0042/2013 from the Brazilian State and Federal governments respectively. Although the multiplicative and growth‐arrested states play key roles in Leishmania development, the regulators of these transitions are largely unknown. In an attempt to gain a better understanding of these processes, we characterised one member of a family of protein kinases with dual specificity, LinDYRK1, which acts as a stasis regulator in other organisms. LinDYRK1 over‐expressing parasites displayed a decrease in proliferation and in cell cycle re‐entry of arrested cells. Parasites lacking LinDYRK1 displayed distinct fitness phenotypes in logarithmic and stationary growth phases. In logarithmic growth‐phase, LinDYRK1‐/‐ parasites proliferated better than control lines, supporting a role of this kinase in stasis, while in stationary growth‐phase, LinDYRK1‐/‐ parasites had important defects as they rounded up, accumulated vacuoles and lipid bodies and displayed subtle but consistent differences in lipid composition. Moreover, they expressed less metacyclic‐enriched transcripts, displayed increased sensitivity to complement lysis and a significant reduction in survival within peritoneal macrophages. The distinct LinDYRK1‐/‐ growth phase phenotypes were mirrored by the distinct LinDYRK1 localisations in logarithmic (mainly in flagellar pocket area and endosomes) and late stationary phase (mitochondrion). Overall, this work provides first evidence for the role of a DYRK family member in sustaining promastigote stationary phase phenotype and infectivity. Postprint
Databáze: OpenAIRE
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