A conserved guided entry of tail-anchored pathway is involved in the trafficking of a subset of membrane proteins in Plasmodium falciparum

Kumar, Tarkeshwar; Maitra, Satarupa; Rahman, Abdur; Bhattacharjee, Souvik

doi:10.1371/journal.ppat.1009595

Cited by 2 publications

(1 citation statement)

References 143 publications

(209 reference statements)

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“…To test the interaction of PfRKIP and PfCDPK1, we employed a proximity biotinylation assay as described earlier [64]. Briefly, asynchronous cultures of transgenic parasite expressing PFRKIPBioID2V5 and PfRKIPcmyc were grown into 75 cm2 flasks at 2% parasitemia and 4% hematocrit.…”

Section: Co-immunoprecipitation Of Pfrkip Using Proximity Labellingmentioning

confidence: 99%

Plasmodium falciparumRaf kinase inhibitor is a lipid binding protein that interacts with CDPK1 and regulates its activity in asexual blood stage

Sharma,

Krishnan,

Negi

et al. 2023

Preprint

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Raf Kinase Inhibitor Protein (RKIP) is an important regulator of MAPK signaling pathway in multicellular eukaryotes. Plasmodium falciparum RKIP (PfRKIP) is a putative phosphatidylethanolamine binding protein (PEBP) that shares limited similarity with Homo sapiens RKIP (HsRKIP). Interestingly, critical components of MAPK pathway are not expressed in malaria parasite and the physiological function of PfRKIP remains unknown. PfRKIP is expressed throughout the asexual schizogony with maximum expression in late schizonts. Interestingly, PfRKIP and HsRKIP show pH dependent differential interaction profiles with various lipids. At physiological pH, PfRKIP show interaction with PE and lipids containing phosphorylated phosphatidylinositol group; however, HsRKIP show no interaction under the same conditions. Mutation of conserved residues in the PEBP domain of PfRKIP decreases its interaction with PI(3)P. Furthermore, our results suggest that PfRKIP leads to increase in the autophosphorylation of PfCDPK1 that leads to transphosphorylation of substrates by PfCDPK1. Using various in vitro and in vivo experiments we have demonstrated the interaction of PfRKIP with PfCDPK1 and have also identified key residues in PfRKIP that play important role in this interaction. Interestingly, locostatin, a specific inhibitor of mammalian RKIP increased the interaction of PfRKIP with PfCDPK1 that perhaps leads to the sequestration of PfCDPK1 in a heterodimeric complex. Importantly, treatment of malaria parasite with locostatin shows dose dependent inhibition of parasite growth. This study suggests that specific inhibitors that modify PfRKIP leading to increase in its interaction with PfCDPK1 may be designed and explored as novel anti-malarial compounds to inhibit malaria parasite growth.

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Section: Co-immunoprecipitation Of Pfrkip Using Proximity Labellingmentioning

confidence: 99%

Plasmodium falciparumRaf kinase inhibitor is a lipid binding protein that interacts with CDPK1 and regulates its activity in asexual blood stage

Sharma,

Krishnan,

Negi

et al. 2023

Preprint

View full text Add to dashboard Cite

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Decrypting the complexity of the human malaria parasite biology through systems biology approaches

Chahine

Roch

2022

Front. Syst. Biol.

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The human malaria parasite, Plasmodium falciparum, is a unicellular protozoan responsible for over half a million deaths annually. With a complex life cycle alternating between human and invertebrate hosts, this apicomplexan is notoriously adept at evading host immune responses and developing resistance to all clinically administered treatments. Advances in omics-based technologies, increased sensitivity of sequencing platforms and enhanced CRISPR based gene editing tools, have given researchers access to more in-depth and untapped information about this enigmatic micro-organism, a feat thought to be infeasible in the past decade. Here we discuss some of the most important scientific achievements made over the past few years with a focus on novel technologies and platforms that set the stage for subsequent discoveries. We also describe some of the systems-based methods applied to uncover gaps of knowledge left through single-omics applications with the hope that we will soon be able to overcome the spread of this life-threatening disease.

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A conserved guided entry of tail-anchored pathway is involved in the trafficking of a subset of membrane proteins in Plasmodium falciparum

Cited by 2 publications

References 143 publications

Plasmodium falciparumRaf kinase inhibitor is a lipid binding protein that interacts with CDPK1 and regulates its activity in asexual blood stage

Plasmodium falciparumRaf kinase inhibitor is a lipid binding protein that interacts with CDPK1 and regulates its activity in asexual blood stage

Decrypting the complexity of the human malaria parasite biology through systems biology approaches

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