scholarly journals Interaction of Plasmodium falciparum Casein kinase 1 (PfCK1) with components of host cell protein trafficking machinery

2019 ◽  
Author(s):  
Mitchell B Batty ◽  
Ralf B Schittenhelm ◽  
Christian Doerig ◽  
Jose Garcia-Bustos
Keyword(s):  
Plasmodium Falciparum ◽  
Membrane Trafficking ◽  
Casein Kinase ◽  
Cell Protein ◽  
Host Proteins ◽  
Extracellular Medium ◽  
Casein Kinase 1 ◽  
Rbc Membrane ◽  
Stage Of Development ◽  
Higher Eukaryotes

AbstractDuring infection, the Plasmodium falciparum casein kinase 1 (PfCK1) is secreted to the extracellular medium and appears on the RBC membrane during trophozoite stage of development. We attempted to identify a mechanism that describes the secretion of PfCK1 and its appearance on the RBC membrane and suspected a mechanism involving multiple host proteins may be utilised. Indeed, we found that the host proteins GTPase-activating protein and Vps9 domain-containing protein (GAPVD1) and Sorting nexin 22 (SNX22), which have described functions in membrane trafficking in higher eukaryotes, consistently co-purify with PfCK1 suggesting the parasite utilises trafficking pathways previously thought to be inactive in RBCs. Further, reciprocal immunoprecipitation experiments with GAPVD1 identified parasite proteins suggestive of a recycling pathway hitherto only described in higher eukaryotes to recycle membrane proteins. Thus, we have identified components of a trafficking pathway involving parasite proteins that act in concert with host proteins which we hypothesise coordinate the trafficking of PfCK1 during infection.

scholarly journals Interaction of Plasmodium falciparum casein kinase 1 with components of host cell protein trafficking machinery

IUBMB Life ◽  
2020 ◽  
Vol 72 (6) ◽  
pp. 1243-1249 ◽  
Author(s):  
Mitchell B. Batty ◽  
Ralf B. Schittenhelm ◽  
Dominique Dorin‐Semblat ◽  
Christian Doerig ◽  
Jose F. Garcia‐Bustos
Keyword(s):  
Plasmodium Falciparum ◽  
Host Cell ◽  
Protein Trafficking ◽  
Casein Kinase ◽  
Cell Protein ◽  
Host Cell Protein ◽  
Casein Kinase 1

Recent Advances in the Development of Casein Kinase 1 Inhibitors

2020 ◽  
Vol 27 ◽  
Author(s):  
Sha-Sha Li ◽  
Yue-Hui Dong ◽  
Zhao-Peng Liu
Keyword(s):  
Membrane Trafficking ◽  
Physicochemical Characterization ◽  
Structural Features ◽  
Casein Kinase ◽  
Casein Kinase 1 ◽  
Cellular Processes ◽  
Damage Repair ◽  
Recent Developments ◽  
Cytoskeleton Dynamics ◽  
Relationship Of

Background: The casein kinase 1 (CK1) family are involved in regulating many cellular processes including membrane trafficking, DNA damage repair, cytoskeleton dynamics, cytoskeleton maintenance and apoptosis. CK1 isoforms especially CK1δ and CK1ε have emerged as important therapeutic target for severe disorders such as Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), familial advanced sleep phase syndrome and cancer. Due to the importance of CK1 for the pathogenesis of disorders, there are great interests in the development of CK1 inhibitors. Method: Using SciFinder® as a tool, the publications about the biology of CK1 and the recent developments of CK1 inhibitors were surveyed with an exclusion on those published as patents. Results: This review presents the current state of knowledge on the development of CK1 inhibitors, including both the synthetic small molecular inhibitors that were divided into 7 categories according to structural features, and the natural compounds. An overview of the advancement of CK1 inhibitors was given, with the introduction of various existing CK1 inhibitors, their inhibitory activities, and the structure-activity relationships. Conclusion: Thorough physicochemical characterization and biological investigations, it is possible to understand structureactivity relationship of CK1 inhibitors, which will contribute to better design and discovery of potent and selective CK1 inhibitors as potential agents for severe disorders such as AD, ALS and cancer.

scholarly journals 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 ◽  
Author(s):  
Daniel Martel ◽  
Stewart Pine ◽  
Katharina Bartsch ◽  
Joachim Clos ◽  
Gerald F. Späth ◽  
...  
Keyword(s):  
Host Cell ◽  
Membrane Trafficking ◽  
Low Complexity ◽  
Casein Kinase ◽  
Subcellular Localisation ◽  
Casein Kinase 1 ◽  
Cellular Processes ◽  
C Terminus ◽  
Wide Range ◽  
Eukaryotic Organisms

AbstractCasein 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.

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