title: Evidence for the Nucleo-Apical Shuttling of a Beta-Catenin Like Plasmodium falciparum Armadillo Repeat Containing Protein.
abstract: Eukaryotic Armadillo (ARM) repeat proteins are multifaceted with prominent roles in cell-cell adhesion, cytoskeletal regulation and intracellular signaling among many others. One such ARM repeat containing protein, ARM Repeats Only (ARO), has recently been demonstrated in both Toxoplasma (TgARO) and Plasmodium (PfARO) parasites to be targeted to the rhoptries during the late asexual stages. TgARO has been implicated to play an important role in rhoptry positioning i.e. directing the rhoptry towards the apical end of the parasite. Here, we report for the first time that PfARO exhibits a DNA binding property and a dynamic sub-cellular localization between the nucleus (early schizont) and rhoptry (late schizont) during the different stages of the asexual blood-stage life cycle. PfARO possesses a putative nuclear export signal (NES) and the nucleo-apical shuttling was sensitive to Leptomycin B (LMB) suggesting that the nuclear export was mediated by CRM1. Importantly, PfARO specifically bound an A-T rich DNA sequence of the P. falciparum Gyrase A (PfgyrA) gene, suggesting that the DNA binding specificity of PfARO is likely due to the AT-richness of the probe. This is a novel functional characteristic that has not been reported previously for any P. falciparum ARM containing protein and suggests a putative role for PfARO in gene regulation. This study describes for the first time a conserved P. falciparum ARM repeat protein with a high degree of functional versatility.
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
authors.forename: Pallabi
authors.initials: P
authors.lastname: Mitra
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
authors.forename: Enna Dogra
authors.initials: ED
authors.lastname: Gupta
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
authors.forename: Tajali
authors.initials: T
authors.lastname: Sahar
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
authors.forename: Alok K
authors.initials: AK
authors.lastname: Pandey
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
authors.forename: Poonam
authors.initials: P
authors.lastname: Dangi
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
authors.forename: K Sony
authors.initials: KS
authors.lastname: Reddy
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
authors.forename: Virander Singh
authors.initials: VS
authors.lastname: Chauhan
authors.affiliation: Laboratory of Malaria and Vaccine Research, School of Biotechnology, Jawaharlal Nehru University, New Delhi, India.
authors.forename: Deepak
authors.initials: D
authors.lastname: Gaur
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000378:metabolism; D000918:Antibody Specificity / Q000187:drug effects; D051186:Armadillo Domain Proteins / Q000737:chemistry / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D017124:Conserved Sequence; D004247:DNA / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006801:Humans; D008018:Life Cycle Stages / Q000187:drug effects; D013058:Mass Spectrometry; D010271:Parasites / Q000187:drug effects / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012995:Solubility; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D000913:Antibodies, Protozoan; D051186:Armadillo Domain Proteins; D015415:Biomarkers; D005231:Fatty Acids, Unsaturated; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D051176:beta Catenin; D004247:DNA; C038753:leptomycin B
references.citation: Infect Immun. 2014 Jan;82(1):152-64
references.pmid: 24126527
references.citation: Nucleic Acids Res. 2012 Apr;40(7):3066-77
references.pmid: 22167473
references.citation: Nature. 2002 Oct 3;419(6906):498-511
references.pmid: 12368864
references.citation: Mol Biochem Parasitol. 2003 Apr 3;127(2):199-203
references.pmid: 12672529
references.citation: Trends Cell Biol. 2003 Sep;13(9):463-71
references.pmid: 12946625
references.citation: Trends Cell Biol. 2004 Sep;14(9):505-14
references.pmid: 15350979
references.citation: Cell Death Dis. 2014;5:e994
references.pmid: 24434517
references.citation: Proc Natl Acad Sci U S A. 2015 Jan 27;112(4):1179-84
references.pmid: 25583518
references.citation: Cell Host Microbe. 2013 Mar 13;13(3):289-301
references.pmid: 23498954
references.citation: Infect Immun. 2013 Feb;81(2):441-51
references.pmid: 23184525
references.citation: PLoS Pathog. 2013 Feb;9(2):e1003162
references.pmid: 23408890
references.citation: Gene. 2000 Apr 4;246(1-2):255-64
references.pmid: 10767547
references.citation: Nature. 2000 Aug 31;406(6799):1009-12
references.pmid: 10984057
references.citation: Nat Cell Biol. 2000 Sep;2(9):653-60
references.pmid: 10980707
references.citation: Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12085-90
references.pmid: 11035805
references.citation: Protein Eng Des Sel. 2004 Jun;17(6):527-36
references.pmid: 15314210
references.citation: Biochemistry. 1975 Oct 21;14(21):4578-83
references.pmid: 1237311
references.citation: Cell. 2012 Jun 8;149(6):1192-205
references.pmid: 22682243
references.citation: Nucleic Acids Res. 2012 Jul;40(12):5313-31
references.pmid: 22379140
references.citation: Traffic. 2012 Oct;13(10):1335-50
references.pmid: 22759070
references.citation: Nature. 2000 Dec 7;408(6813):727-31
references.pmid: 11130075
references.citation: J Parasitol. 1979 Jun;65(3):418-20
references.pmid: 383936
references.citation: J Antibiot (Tokyo). 1983 Jun;36(6):639-45
references.pmid: 6874585
references.citation: Cell. 1994 Mar 11;76(5):789-91
references.pmid: 7907279
references.citation: Cell. 1997 Sep 5;90(5):871-82
references.pmid: 9298899
references.citation: Cell. 1997 Sep 19;90(6):1051-60
references.pmid: 9323133
references.citation: Curr Biol. 1998 Feb 12;8(4):181-90
references.pmid: 9501980
references.citation: Exp Cell Res. 1998 Aug 1;242(2):540-7
references.pmid: 9683540
references.citation: Oncogene. 1999 Oct 7;18(41):5654-61
references.pmid: 10523845
references.citation: Int J Parasitol. 2004 Dec;34(13-14):1413-29
references.pmid: 15582519
references.citation: J Mol Biol. 2005 Feb 11;346(1):367-76
references.pmid: 15663951
references.citation: Cell. 2005 Apr 8;121(1):25-36
references.pmid: 15820676
references.citation: Cell. 2005 Jun 3;121(5):761-72
references.pmid: 15935762
references.citation: Biochim Biophys Acta. 2007 Jan;1773(1):59-68
references.pmid: 17050009
references.citation: Nucleic Acids Res. 2007 Jan;35(Database issue):D427-30
references.pmid: 17098930
references.citation: J Cell Sci. 2007 Oct 1;120(Pt 19):3337-44
references.pmid: 17881495
references.citation: Proc Natl Acad Sci U S A. 2007 Nov 6;104(45):17789-94
references.pmid: 17971435
references.citation: EMBO J. 2008 Oct 22;27(20):2746-56
references.pmid: 18818695
references.citation: Nat Protoc. 2009;4(3):363-71
references.pmid: 19247286
references.citation: Dev Cell. 2009 Jul;17(1):9-26
references.pmid: 19619488
references.citation: Eukaryot Cell. 2009 Sep;8(9):1341-51
references.pmid: 19633266
references.citation: Cold Spring Harb Perspect Biol. 2009 Aug;1(2):a002881
references.pmid: 20066091
references.citation: Trends Cell Biol. 2010 Aug;20(8):470-81
references.pmid: 20688255
references.citation: PLoS One. 2010;5(9):e12901
references.pmid: 20886115
references.citation: PLoS One. 2011;6(2):e17102
references.pmid: 21386888
references.citation: Curr Opin Microbiol. 2011 Aug;14(4):422-8
references.pmid: 21803641
references.citation: Lancet. 2012 Feb 4;379(9814):413-31
references.pmid: 22305225
references.citation: J Cell Biol. 2012 Sep 17;198(6):961-71
references.pmid: 22986493