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LEISHMANIA DUAL-SPECIFICITY TYROSINE-REGULATED KINASE 1 (DYRK1) IS REQUIRED FOR SUSTAINING LEISHMANIA STATIONARY PHASE PHENOTYPE
Autor(es)
Afiliação
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil.
Institut Pasteur and INSERM. Unité de Parasitologie Moléculaire et Signalisation. Department of Parasites and Insect Vectors. Paris, France.
The University of St. Andrews. School of Biology. Biomedical Sciences Research Complex. St. Andrews, UK.
Hellenic Pasteur Institute. Molecular Parasitology Laboratory, Microbiology Department. Athens, Greece.
Hellenic Pasteur Institute. Molecular Parasitology Laboratory, Microbiology Department. Athens, Greece.
Institut Pasteur and INSERM. Unité de Parasitologie Moléculaire et Signalisation. Department of Parasites and Insect Vectors. Paris, France.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil.
Hellenic Pasteur Institute. Molecular Parasitology Laboratory, Microbiology Department. Athens, Greece.
Institut Pasteur and INSERM. Unité de Parasitologie Moléculaire et Signalisation. Department of Parasites and Insect Vectors. Paris, France.
The University of St. Andrews. School of Biology. Biomedical Sciences Research Complex. St. Andrews, UK.
Hellenic Pasteur Institute. Molecular Parasitology Laboratory, Microbiology Department. Athens, Greece.
Hellenic Pasteur Institute. Molecular Parasitology Laboratory, Microbiology Department. Athens, Greece.
Institut Pasteur and INSERM. Unité de Parasitologie Moléculaire et Signalisation. Department of Parasites and Insect Vectors. Paris, France.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil.
Hellenic Pasteur Institute. Molecular Parasitology Laboratory, Microbiology Department. Athens, Greece.
Resumo em Inglês
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 overexpressing 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–/– p arasites h ad i mportant d efects a s t hey r ounded u p, a ccumulated
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–/– g rowth p hase p henotypes
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.
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