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Published in: Malaria Journal 1/2009

Open Access 01-12-2009 | Research

Expression of GIMAP1, a GTPase of the immunity-associated protein family, is not up-regulated in malaria

Authors: Amy Saunders, Tracey Lamb, John Pascall, Amanda Hutchings, Carine Dion, Christine Carter, Lucy Hepburn, Jean Langhorne, Geoffrey W Butcher

Published in: Malaria Journal | Issue 1/2009

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Abstract

Background

GIMAP (GTPase of the immunity-associated protein family) proteins are a family of putative GTPases believed to be regulators of cell death in lymphomyeloid cells. GIMAP1 was the first reported member of this gene family, identified as a gene up-regulated at the RNA level in the spleens of mice infected with the malarial parasite, Plasmodium chabaudi.

Methods

A monoclonal antibody against mouse GIMAP1 was developed and was used to analyse the expression of the endogenous protein in tissues of normal mice and in defined sub-populations of cells prepared from lymphoid tissues using flow cytometry. It was also used to assess the expression of GIMAP1 protein after infection and/or immunization of mice with P. chabaudi. Real-time PCR analysis was employed to measure the expression of GIMAP1 for comparison with the protein level analysis.

Results

GIMAP1 protein expression was detected in all lineages of lymphocytes (T, B, NK), in F4/80+ splenic macrophages and in some lymphoid cell lines. Additional evidence is presented suggesting that the strong expression by mature B cells of GIMAP1 and other GIMAP genes and proteins seen in mice may be a species-dependent characteristic. Unexpectedly, no increase was found in the expression of GIMAP1 in P. chabaudi infected mice at either the mRNA or protein level, and this remained so despite applying a number of variations to the protocol.

Conclusion

The model of up-regulation of GIMAP1 in response to infection/immunization with P. chabaudi is not a robustly reproducible experimental system. The GIMAP1 protein is widely expressed in lymphoid cells, with an interesting increase in expression in the later stages of B cell development. Alternative approaches will be required to define the functional role of this GTPase in immune cells.
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Literature
1.
go back to reference Krücken J, Schmitt-Wrede HP, Markmann-Mulisch U, Wunderlich F: Novel gene expressed in spleen cells mediating acquired testosterone-resistant immunity to Plasmodium chabaudi malaria. Biochem Biophys Res Commun. 1997, 230: 167-170. 10.1006/bbrc.1996.5876.CrossRefPubMed Krücken J, Schmitt-Wrede HP, Markmann-Mulisch U, Wunderlich F: Novel gene expressed in spleen cells mediating acquired testosterone-resistant immunity to Plasmodium chabaudi malaria. Biochem Biophys Res Commun. 1997, 230: 167-170. 10.1006/bbrc.1996.5876.CrossRefPubMed
2.
go back to reference Krücken J, Schroetel RM, Müller IU, Saïdani N, Marinovski P, Benten WP, Stamm O, Wunderlich F: Comparative analysis of the human gimap gene cluster encoding a novel GTPase family. Gene. 2004, 341: 291-304. 10.1016/j.gene.2004.07.005.CrossRefPubMed Krücken J, Schroetel RM, Müller IU, Saïdani N, Marinovski P, Benten WP, Stamm O, Wunderlich F: Comparative analysis of the human gimap gene cluster encoding a novel GTPase family. Gene. 2004, 341: 291-304. 10.1016/j.gene.2004.07.005.CrossRefPubMed
3.
go back to reference Liu C, Wang T, Zhang W, Li X: Computational identification and analysis of immune-associated nucleotide gene family in Arabidopsis thaliana. J Plant Physiol. 2008, 165: 777-787. 10.1016/j.jplph.2007.06.002.CrossRefPubMed Liu C, Wang T, Zhang W, Li X: Computational identification and analysis of immune-associated nucleotide gene family in Arabidopsis thaliana. J Plant Physiol. 2008, 165: 777-787. 10.1016/j.jplph.2007.06.002.CrossRefPubMed
4.
go back to reference Nitta T, Nasreen M, Seike T, Goji A, Ohigashi I, Miyazaki T, Ohta T, Kanno M, Takahama Y: IAN family critically regulates survival and development of T lymphocytes. PLoS Biol. 2006, 4: e103-10.1371/journal.pbio.0040103.PubMedCentralCrossRefPubMed Nitta T, Nasreen M, Seike T, Goji A, Ohigashi I, Miyazaki T, Ohta T, Kanno M, Takahama Y: IAN family critically regulates survival and development of T lymphocytes. PLoS Biol. 2006, 4: e103-10.1371/journal.pbio.0040103.PubMedCentralCrossRefPubMed
5.
go back to reference Reuber TL, Ausubel FM: Isolation of Arabidopsis genes that differentiate between resistance responses mediated by the RPS2 and RPM1 disease resistance genes. Plant Cell. 1996, 8: 241-249. 10.1105/tpc.8.2.241.PubMedCentralCrossRefPubMed Reuber TL, Ausubel FM: Isolation of Arabidopsis genes that differentiate between resistance responses mediated by the RPS2 and RPM1 disease resistance genes. Plant Cell. 1996, 8: 241-249. 10.1105/tpc.8.2.241.PubMedCentralCrossRefPubMed
6.
go back to reference Krücken J, Stamm O, Schmitt-Wrede HP, Mincheva A, Lichter P, Wunderlich F: Spleen-specific expression of the malaria-inducible intronless mouse gene imap38. J Biol Chem. 1999, 274: 24383-24391. 10.1074/jbc.274.34.24383.CrossRefPubMed Krücken J, Stamm O, Schmitt-Wrede HP, Mincheva A, Lichter P, Wunderlich F: Spleen-specific expression of the malaria-inducible intronless mouse gene imap38. J Biol Chem. 1999, 274: 24383-24391. 10.1074/jbc.274.34.24383.CrossRefPubMed
7.
go back to reference Hernández-Hoyos G, Joseph S, Miller NG, Butcher GW: The lymphopenia mutation of the BB rat causes inappropriate apoptosis of mature thymocytes. Eur J Immunol. 1999, 29: 1832-1841. 10.1002/(SICI)1521-4141(199906)29:06<1832::AID-IMMU1832>3.0.CO;2-F.CrossRefPubMed Hernández-Hoyos G, Joseph S, Miller NG, Butcher GW: The lymphopenia mutation of the BB rat causes inappropriate apoptosis of mature thymocytes. Eur J Immunol. 1999, 29: 1832-1841. 10.1002/(SICI)1521-4141(199906)29:06<1832::AID-IMMU1832>3.0.CO;2-F.CrossRefPubMed
8.
go back to reference Pandarpurkar M, Wilson-Fritch L, Corvera S, Markholst H, Hornum L, Greiner DL, Mordes JP, Rossini AA, Bortell R: Ian4 is required for mitochondrial integrity and T cell survival. Proc Natl Acad Sci USA. 2003, 100: 10382-10387. 10.1073/pnas.1832170100.PubMedCentralCrossRefPubMed Pandarpurkar M, Wilson-Fritch L, Corvera S, Markholst H, Hornum L, Greiner DL, Mordes JP, Rossini AA, Bortell R: Ian4 is required for mitochondrial integrity and T cell survival. Proc Natl Acad Sci USA. 2003, 100: 10382-10387. 10.1073/pnas.1832170100.PubMedCentralCrossRefPubMed
9.
go back to reference Ramanathan S, Norwich K, Poussier P: Antigen activation rescues recent thymic emigrants from programmed cell death in the BB rat. J Immunol. 1998, 160: 5757-5764.PubMed Ramanathan S, Norwich K, Poussier P: Antigen activation rescues recent thymic emigrants from programmed cell death in the BB rat. J Immunol. 1998, 160: 5757-5764.PubMed
10.
go back to reference Sandal T, Aumo L, Hedin L, Gjertsen BT, Doskeland SO: Irod/Ian5: an inhibitor of gamma-radiation- and okadaic acid-induced apoptosis. Mol Biol Cell. 2003, 14: 3292-3304. 10.1091/mbc.E02-10-0700.PubMedCentralCrossRefPubMed Sandal T, Aumo L, Hedin L, Gjertsen BT, Doskeland SO: Irod/Ian5: an inhibitor of gamma-radiation- and okadaic acid-induced apoptosis. Mol Biol Cell. 2003, 14: 3292-3304. 10.1091/mbc.E02-10-0700.PubMedCentralCrossRefPubMed
11.
go back to reference Schulteis RD, Chu H, Dai X, Chen Y, Edwards B, Haribhai D, Williams CB, Malarkannan S, Hessner MJ, Glisic-Milosavljevic S, Jana S, Kerschen EJ, Ghosh S, Wang D, Kwitek AE, Lernmark A, Gorski J, Weiler H: Impaired survival of peripheral T cells, disrupted NK/NKT cell development, and liver failure in mice lacking gimap5. Blood. 2008, 112 (13): 4905-14. 10.1182/blood-2008-03-146555.PubMedCentralCrossRefPubMed Schulteis RD, Chu H, Dai X, Chen Y, Edwards B, Haribhai D, Williams CB, Malarkannan S, Hessner MJ, Glisic-Milosavljevic S, Jana S, Kerschen EJ, Ghosh S, Wang D, Kwitek AE, Lernmark A, Gorski J, Weiler H: Impaired survival of peripheral T cells, disrupted NK/NKT cell development, and liver failure in mice lacking gimap5. Blood. 2008, 112 (13): 4905-14. 10.1182/blood-2008-03-146555.PubMedCentralCrossRefPubMed
12.
go back to reference Carter C, Dion C, Schnell S, Coadwell WJ, Graham M, Hepburn L, Morgan G, Hutchings A, Pascall JC, Jacobs H: A natural hypomorphic variant of the apoptosis regulator Gimap4/IAN1. J Immunol. 2007, 179: 1784-1795.CrossRefPubMed Carter C, Dion C, Schnell S, Coadwell WJ, Graham M, Hepburn L, Morgan G, Hutchings A, Pascall JC, Jacobs H: A natural hypomorphic variant of the apoptosis regulator Gimap4/IAN1. J Immunol. 2007, 179: 1784-1795.CrossRefPubMed
13.
go back to reference Schnell S, Demolliere C, Berk van den P, Jacobs H: Gimap4 accelerates T-cell death. Blood. 2006, 108: 591-599. 10.1182/blood-2005-11-4616.CrossRefPubMed Schnell S, Demolliere C, Berk van den P, Jacobs H: Gimap4 accelerates T-cell death. Blood. 2006, 108: 591-599. 10.1182/blood-2005-11-4616.CrossRefPubMed
14.
go back to reference Galfrè G, Milstein C, Wright B: Rat × rat hybrid myelomas and a monoclonal anti-Fd portion of mouse IgG. Nature. 1979, 277: 131-133. 10.1038/277131a0.CrossRefPubMed Galfrè G, Milstein C, Wright B: Rat × rat hybrid myelomas and a monoclonal anti-Fd portion of mouse IgG. Nature. 1979, 277: 131-133. 10.1038/277131a0.CrossRefPubMed
15.
go back to reference Dion C, Carter C, Hepburn L, Coadwell WJ, Morgan G, Graham M, Pugh N, Anderson G, Butcher GW, Miller JR: Expression of the Ian family of putative GTPases during T cell development and description of an Ian with three sets of GTP/GDP-binding motifs. Int Immunol. 2005, 17: 1257-1268. 10.1093/intimm/dxh302.CrossRefPubMed Dion C, Carter C, Hepburn L, Coadwell WJ, Morgan G, Graham M, Pugh N, Anderson G, Butcher GW, Miller JR: Expression of the Ian family of putative GTPases during T cell development and description of an Ian with three sets of GTP/GDP-binding motifs. Int Immunol. 2005, 17: 1257-1268. 10.1093/intimm/dxh302.CrossRefPubMed
16.
go back to reference Walliker D, Carter R, Sanderson A: Genetic studies on Plasmodium chabaudi: recombination between enzyme markers. Parasitology. 1975, 70: 19-24.CrossRefPubMed Walliker D, Carter R, Sanderson A: Genetic studies on Plasmodium chabaudi: recombination between enzyme markers. Parasitology. 1975, 70: 19-24.CrossRefPubMed
17.
go back to reference Meding SJ, Cheng SC, Simon-Haarhaus B, Langhorne J: Role of gamma interferon during infection with Plasmodium chabaudi chabaudi. Infect Immun. 1990, 58: 3671-3678.PubMedCentralPubMed Meding SJ, Cheng SC, Simon-Haarhaus B, Langhorne J: Role of gamma interferon during infection with Plasmodium chabaudi chabaudi. Infect Immun. 1990, 58: 3671-3678.PubMedCentralPubMed
18.
go back to reference Langhorne J, Gillard S, Simon B, Slade S, Eichmann K: Frequencies of CD4+ T cells reactive with Plasmodium chabaudi chabaudi: distinct response kinetics for cells with Th1 and Th2 characteristics during infection. Int Immunol. 1989, 1: 416-424. 10.1093/intimm/1.4.416.CrossRefPubMed Langhorne J, Gillard S, Simon B, Slade S, Eichmann K: Frequencies of CD4+ T cells reactive with Plasmodium chabaudi chabaudi: distinct response kinetics for cells with Th1 and Th2 characteristics during infection. Int Immunol. 1989, 1: 416-424. 10.1093/intimm/1.4.416.CrossRefPubMed
19.
go back to reference Wunderlich F, Helwig M, Schillinger G, Vial H, Philippot J, Speth V: Isolation and characterization of parasites and host cell ghosts from erythrocytes infected with Plasmodium chabaudi. Mol Biochem Parasitol. 1987, 23: 103-115. 10.1016/0166-6851(87)90145-9.CrossRefPubMed Wunderlich F, Helwig M, Schillinger G, Vial H, Philippot J, Speth V: Isolation and characterization of parasites and host cell ghosts from erythrocytes infected with Plasmodium chabaudi. Mol Biochem Parasitol. 1987, 23: 103-115. 10.1016/0166-6851(87)90145-9.CrossRefPubMed
20.
go back to reference LaBelle JL, Truitt RL: Characterization of a murine NKT cell tumor previously described as an acute myelogenous leukemia. Leuk Lymphoma. 2002, 43: 1637-1644. 10.1080/1042819021000002974.CrossRefPubMed LaBelle JL, Truitt RL: Characterization of a murine NKT cell tumor previously described as an acute myelogenous leukemia. Leuk Lymphoma. 2002, 43: 1637-1644. 10.1080/1042819021000002974.CrossRefPubMed
21.
go back to reference Nitta T, Takahama Y: The lymphocyte guard-IANs: regulation of lymphocyte survival by IAN/GIMAP family proteins. Trends Immunol. 2007, 28: 58-65. 10.1016/j.it.2006.12.002.CrossRefPubMed Nitta T, Takahama Y: The lymphocyte guard-IANs: regulation of lymphocyte survival by IAN/GIMAP family proteins. Trends Immunol. 2007, 28: 58-65. 10.1016/j.it.2006.12.002.CrossRefPubMed
22.
go back to reference Hornum L, Romer J, Markholst H: The diabetes-prone BB rat carries a frameshift mutation in Ian4, a positional candidate of Iddm1. Diabetes. 2002, 51: 1972-1979. 10.2337/diabetes.51.6.1972.CrossRefPubMed Hornum L, Romer J, Markholst H: The diabetes-prone BB rat carries a frameshift mutation in Ian4, a positional candidate of Iddm1. Diabetes. 2002, 51: 1972-1979. 10.2337/diabetes.51.6.1972.CrossRefPubMed
23.
go back to reference MacMurray AJ, Moralejo DH, Kwitek AE, Rutledge EA, Van Yserloo B, Gohlke P, Speros SJ, Snyder B, Schaefer J, Bieg S, Jiang J, Ettinger RA, Fuller J, Daniels TL, Pettersson A, Orlebeke K, Birren B, Jacob HJ, Lander ES, Lernmark A: Lymphopenia in the BB rat model of type 1 diabetes is due to a mutation in a novel immune-associated nucleotide (Ian)-related gene. Genome Res. 2002, 12: 1029-1039. 10.1101/gr.412702.PubMedCentralCrossRefPubMed MacMurray AJ, Moralejo DH, Kwitek AE, Rutledge EA, Van Yserloo B, Gohlke P, Speros SJ, Snyder B, Schaefer J, Bieg S, Jiang J, Ettinger RA, Fuller J, Daniels TL, Pettersson A, Orlebeke K, Birren B, Jacob HJ, Lander ES, Lernmark A: Lymphopenia in the BB rat model of type 1 diabetes is due to a mutation in a novel immune-associated nucleotide (Ian)-related gene. Genome Res. 2002, 12: 1029-1039. 10.1101/gr.412702.PubMedCentralCrossRefPubMed
24.
go back to reference Dahéron L, Zenz T, Siracusa LD, Brenner C, Calabretta B: Molecular cloning of Ian4: a BCR/ABL-induced gene that encodes an outer membrane mitochondrial protein with GTP-binding activity. Nucleic Acids Res. 2001, 29: 1308-1316. 10.1093/nar/29.6.1308.PubMedCentralCrossRefPubMed Dahéron L, Zenz T, Siracusa LD, Brenner C, Calabretta B: Molecular cloning of Ian4: a BCR/ABL-induced gene that encodes an outer membrane mitochondrial protein with GTP-binding activity. Nucleic Acids Res. 2001, 29: 1308-1316. 10.1093/nar/29.6.1308.PubMedCentralCrossRefPubMed
26.
go back to reference Poirier GM, Anderson G, Huvar A, Wagaman PC, Shuttleworth J, Jenkinson E, Jackson MR, Peterson PA, Erlander MG: Immune-associated nucleotide-1 (IAN-1) is a thymic selection marker and defines a novel gene family conserved in plants. J Immunol. 1999, 163: 4960-4969.PubMed Poirier GM, Anderson G, Huvar A, Wagaman PC, Shuttleworth J, Jenkinson E, Jackson MR, Peterson PA, Erlander MG: Immune-associated nucleotide-1 (IAN-1) is a thymic selection marker and defines a novel gene family conserved in plants. J Immunol. 1999, 163: 4960-4969.PubMed
27.
go back to reference Epe M: Funktionale characterisierung von murinen gimap genen. Dissertation: Heinrich-Heine-Universitat, Dusseldorf. 2004, Deutsche Nationalbibliothek Archivserver deposit.d-nb.de Epe M: Funktionale characterisierung von murinen gimap genen. Dissertation: Heinrich-Heine-Universitat, Dusseldorf. 2004, Deutsche Nationalbibliothek Archivserver deposit.d-nb.de
28.
go back to reference Kannan K, Kaminski N, Rechavi G, Jakob-Hirsch J, Amariglio N, Givol D: DNA microarray analysis of genes involved in p53 mediated apoptosis: activation of Apaf-1. Oncogene. 2001, 20: 3449-3455. 10.1038/sj.onc.1204446.CrossRefPubMed Kannan K, Kaminski N, Rechavi G, Jakob-Hirsch J, Amariglio N, Givol D: DNA microarray analysis of genes involved in p53 mediated apoptosis: activation of Apaf-1. Oncogene. 2001, 20: 3449-3455. 10.1038/sj.onc.1204446.CrossRefPubMed
29.
go back to reference Stevenson MM, Lyanga JJ, Skamene E: Murine malaria: genetic control of resistance to Plasmodium chabaudi. Infect Immun. 1982, 38: 80-88.PubMedCentralPubMed Stevenson MM, Lyanga JJ, Skamene E: Murine malaria: genetic control of resistance to Plasmodium chabaudi. Infect Immun. 1982, 38: 80-88.PubMedCentralPubMed
Metadata
Title
Expression of GIMAP1, a GTPase of the immunity-associated protein family, is not up-regulated in malaria
Authors
Amy Saunders
Tracey Lamb
John Pascall
Amanda Hutchings
Carine Dion
Christine Carter
Lucy Hepburn
Jean Langhorne
Geoffrey W Butcher
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2009
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-8-53

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