The low complexity regions in the C-terminus are essential for the subcellular localisation of Leishmania casein kinase 1 but not for its activity

Daniel Martel (1, 2) , Stewart Pine (1) , Katharina Bartsch (3) , Joachim Clos (3) , Gerald Späth (1) , Najma Rachidi (1)

1 Parasitologie moléculaire et Signalisation / Molecular Parasitology and Signaling
2 USPC - Université Sorbonne Paris Cité
3 BNITM - Bernhard Nocht Institute for Tropical Medicine - Bernhard-Nocht-Institut für Tropenmedizin [Hamburg, Germany]

Casein Kinase 1 (CK1) family members are serine/threonine protein kinases ubiquitously expressed in eukaryotic organisms. They are involved in a wide range of important cellular processes, such as membrane trafficking, or vesicular transport in organisms from yeast to humans. Due to its broad spectrum of action, CK1 activity and expression is tightly regulated by a number of mechanisms, including subcellular sequestration. Defects in CK1 regulation, localisation or the introduction of mutations in the CK1 coding sequence are often associated with important diseases such as cancer. Increasing evidence suggest that the manipulation of host cell CK1 signalling pathways by intracellular pathogens, either by exploiting the host CK1 or by exporting the CK1 of the pathogen into the host cell may play an important role in infectious diseases. Leishmania CK1.2 is essential for parasite survival and released into the host cell, playing an important role in host pathogen interactions. Although Leishmania CK1.2 has dual role in the parasite and in the host cell, nothing is known about its parasitic localisation and organelle-specific functions. In this study, we show that CK1.2 is a ubiquitous kinase, which is present in the cytoplasm, associated to the cytoskeleton and localised to various organelles, indicating potential roles in kinetoplast and nuclear segregation, as well as ribosomal processing and motility. Furthermore, using truncated mutants, we show for the first time that the two low complexity regions (LCR) present in the C-terminus of CK1.2 are essential for the subcellular localisation of CK1.2 but not for its kinase activity, whereas the deletion of the N-terminus leads to a dramatic decrease in CK1.2 abundance. In conclusion, our data on the localisation and regulation of Leishmania CK1.2 contribute to increase the knowledge on this essential kinase and get insights into its role in the parasite.

Domaines: Parasitologie; Biochimie, Biologie Moléculaire

Daniel Martel, Stewart Pine, Katharina Bartsch, Joachim Clos, Gerald Späth, et al.. The low complexity regions in the C-terminus are essential for the subcellular localisation of Leishmania casein kinase 1 but not for its activity. 2020. ⟨pasteur-02874585⟩