title: Plasmodium falciparum signal recognition particle components and anti-parasitic effect of ivermectin in blocking nucleo-cytoplasmic shuttling of SRP.
abstract: Signal recognition particle (SRP) is a ubiquitous ribonucleoprotein complex that targets proteins to endoplasmic reticulum (ER) in eukaryotes. Here we report that Plasmodium falciparum SRP is composed of six polypeptides; SRP9, SRP14, SRP19, SRP54, SRP68 and SRP72 and a 303nt long SRP RNA. We generated four transgenic parasite lines expressing SRP-GFP chimeric proteins and co-localization studies showed the nucleo-cytoplasmic localization for these proteins. The evaluation of the effect of known SRP and nuclear import/export inhibitors on P. falciparum revealed that ivermectin, an inhibitor of importin α/β mediated nuclear import inhibited the nuclear import of PfSRP polypeptides at submicromolar concentration, thereby killing the parasites. These findings provide insights into dynamic structure of P. falciparum SRP and also raise the possibility that ivermectin could be used in combination with other antimalarial agents to control the disease.
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology, P. O. Box 10504, Aruna Asaf Ali Marg, New Delhi, 110067, India.
authors.forename: M
authors.initials: M
authors.lastname: Panchal
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology, P. O. Box 10504, Aruna Asaf Ali Marg, New Delhi, 110067, India.
authors.forename: K
authors.initials: K
authors.lastname: Rawat
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology, P. O. Box 10504, Aruna Asaf Ali Marg, New Delhi, 110067, India.
authors.forename: G
authors.initials: G
authors.lastname: Kumar
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology, P. O. Box 10504, Aruna Asaf Ali Marg, New Delhi, 110067, India.
authors.forename: K M
authors.initials: KM
authors.lastname: Kibria
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology, P. O. Box 10504, Aruna Asaf Ali Marg, New Delhi, 110067, India.
authors.forename: S
authors.initials: S
authors.lastname: Singh
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology, P. O. Box 10504, Aruna Asaf Ali Marg, New Delhi, 110067, India.
authors.forename: Md
authors.initials: M
authors.lastname: Kalamuddin
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology, P. O. Box 10504, Aruna Asaf Ali Marg, New Delhi, 110067, India.
authors.forename: A
authors.initials: A
authors.lastname: Mohmmed
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology, P. O. Box 10504, Aruna Asaf Ali Marg, New Delhi, 110067, India.
authors.forename: P
authors.initials: P
authors.lastname: Malhotra
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology, P. O. Box 10504, Aruna Asaf Ali Marg, New Delhi, 110067, India.
authors.forename: R
authors.initials: R
authors.lastname: Tuteja
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007559:Ivermectin / Q000494:pharmacology*; D016778:Malaria, Falciparum / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D018271:Signal Recognition Particle / Q000235:genetics / Q000378:metabolism*
chemical_list: D000981:Antiprotozoal Agents; D015800:Protozoan Proteins; D018271:Signal Recognition Particle; D007559:Ivermectin