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Irgm1 (LRG-47), a regulator of cell-autonomous immunity, does not localize to mycobacterial or listerial phagosomes in IFN-γ-induced mouse cells.

Publication ,  Journal Article
Springer, HM; Schramm, M; Taylor, GA; Howard, JC
Published in: J Immunol
August 15, 2013

The IFN-inducible protein Irgm1 (LRG-47) belongs to the family of immunity-related GTPases that function in cell-autonomous resistance against intracellular pathogens in mice. Irgm1 deficiency is associated with a severe immunodeficiency syndrome. The protein has been variously interpreted as a direct effector molecule on bacterial phagosomes or on other organelles or as an inducer of autophagy. In this study, we re-examined one of these claims, namely that Irgm1 targets mycobacterial and listerial phagosomes. We found no colocalization of endogenous Irgm1, using two immunofluorescent staining techniques, either in fibroblasts or in macrophages. We demonstrated the predicted existence of two protein isoforms of Irgm1 derived from differential splicing and described immunological reagents for their detection. Both Irgm1 isoforms localize to the Golgi apparatus and weakly to mitochondria; however, only the long Irgm1 isoforms can be detected on endolysosomal membranes. Together with the previous observation that the general immunodeficiency phenotype of Irgm1(-/-) mice is reversed in Irgm1/Irgm3 double-deficient mice, our results argue against a direct effector function of Irgm1 at the bacterial phagosome. We discuss these findings in the context of evidence that Irgm1 functions as a negative regulator of other members of the immunity-related GTPase protein family.

Duke Scholars

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

August 15, 2013

Volume

191

Issue

4

Start / End Page

1765 / 1774

Location

United States

Related Subject Headings

  • Protein Isoforms
  • Phagosomes
  • Peptide Fragments
  • Mycobacterium bovis
  • Molecular Sequence Data
  • Mitochondria
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Macrophages
 

Citation

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Springer, H. M., Schramm, M., Taylor, G. A., & Howard, J. C. (2013). Irgm1 (LRG-47), a regulator of cell-autonomous immunity, does not localize to mycobacterial or listerial phagosomes in IFN-γ-induced mouse cells. J Immunol, 191(4), 1765–1774. https://doi.org/10.4049/jimmunol.1300641
Springer, Helen M., Michael Schramm, Gregory A. Taylor, and Jonathan C. Howard. “Irgm1 (LRG-47), a regulator of cell-autonomous immunity, does not localize to mycobacterial or listerial phagosomes in IFN-γ-induced mouse cells.J Immunol 191, no. 4 (August 15, 2013): 1765–74. https://doi.org/10.4049/jimmunol.1300641.
Springer, Helen M., et al. “Irgm1 (LRG-47), a regulator of cell-autonomous immunity, does not localize to mycobacterial or listerial phagosomes in IFN-γ-induced mouse cells.J Immunol, vol. 191, no. 4, Aug. 2013, pp. 1765–74. Pubmed, doi:10.4049/jimmunol.1300641.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

August 15, 2013

Volume

191

Issue

4

Start / End Page

1765 / 1774

Location

United States

Related Subject Headings

  • Protein Isoforms
  • Phagosomes
  • Peptide Fragments
  • Mycobacterium bovis
  • Molecular Sequence Data
  • Mitochondria
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Macrophages