title: Receptor for Activated C-Kinase 1 (PfRACK1) is required for Plasmodium falciparum intra-erythrocytic proliferation.
abstract: Emerging resistance to current anti-malarials necessitates a more detailed understanding of the biological processes of Plasmodium falciparum proliferation, thus allowing identification of new drug targets. The well-conserved protein Receptor for Activated C-Kinase 1 (RACK1) was originally identified in mammalian cells as an anchoring protein for protein kinase C (PKC) and has since been shown to be important for cell migration, cytokinesis, transcription, epigenetics, and protein translation. The P. falciparum ortholog, PfRACK1, is expressed in blood stages of the parasite and is diffusely localized in the parasite cytoplasm. Using a destabilizing domain to allow inducible knockdown of the endogenous protein level, we evaluated the requirement for PfRACK1 during blood-stage replication. Following destabilization, the parasites demonstrate a nearly complete growth arrest at the trophozoite stage. The essential nature of PfRACK1 suggests that the protein itself or the pathways regulated by the protein are potential targets for novel anti-malarial therapeutics.
authors.affiliation: Boston Children's Hospital, Division of Infectious Diseases, Boston, MA 02115, USA; Harvard Medical School, Department of Pediatrics, Boston, MA 02115, USA; Karolinska Institutet, Department of Microbiology, Tumor and Cell Biology, 171 77 Stockholm, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Blomqvist
authors.affiliation: Boston Children's Hospital, Division of Infectious Diseases, Boston, MA 02115, USA; Harvard Medical School, Department of Pediatrics, Boston, MA 02115, USA.
authors.forename: Christen
authors.initials: C
authors.lastname: DiPetrillo
authors.affiliation: Boston Children's Hospital, Division of Infectious Diseases, Boston, MA 02115, USA; Harvard Medical School, Department of Pediatrics, Boston, MA 02115, USA.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Streva
authors.affiliation: Boston Children's Hospital, Division of Infectious Diseases, Boston, MA 02115, USA; Harvard Medical School, Department of Pediatrics, Boston, MA 02115, USA.
authors.forename: Stewart
authors.initials: S
authors.lastname: Pine
authors.affiliation: Boston Children's Hospital, Division of Infectious Diseases, Boston, MA 02115, USA; Harvard Medical School, Department of Pediatrics, Boston, MA 02115, USA. Electronic address: jeffrey.dvorin@childrens.harvard.edu.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Dvorin
mesh_terms: D004912:Erythrocytes / Q000469:parasitology*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D008018:Life Cycle Stages; D016778:Malaria, Falciparum / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface
keywords: Malaria; Plasmodium falciparum; Receptor of Activated C-Kinase 1 (RACK1)