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Immunity-related GTPase M (IRGM) proteins influence the localization of guanylate-binding protein 2 (GBP2) by modulating macroautophagy.

Publication ,  Journal Article
Traver, MK; Henry, SC; Cantillana, V; Oliver, T; Hunn, JP; Howard, JC; Beer, S; Pfeffer, K; Coers, J; Taylor, GA
Published in: J Biol Chem
September 2, 2011

The immunity-related GTPases (IRGs) are a family of proteins induced by interferon-γ that play a crucial role in innate resistance to intracellular pathogens. The M subfamily of IRG proteins (IRGM) plays a profound role in this context, in part because of the ability of its members to regulate the localization and expression of other IRG proteins. We present here evidence that IRGM proteins affect the localization of the guanylate-binding proteins (GBPs), a second family of interferon-induced GTP-binding proteins that also function in innate immunity. Absence of Irgm1 or Irgm3 led to accumulation of Gbp2 in intracellular compartments that were positive for both the macroautophagy (hereafter referred to as autophagy) marker LC3 and the autophagic adapter molecule p62/Sqstm1. Gbp2 was similarly relocalized in cells in which autophagy was impaired because of the absence of Atg5. Both in Atg5- and IRGM-deficient cells, the IRG protein Irga6 relocalized to the same compartments as Gbp2, raising the possibility of a common regulatory mechanism. However, other data indicated that Irga6, but not Gbp2, was ubiquitinated in IRGM-deficient cells. Similarly, coimmunoprecipitation studies indicated that although Irgm3 did interact directly with Irgb6, it did not interact with Gbp2. Collectively, these data suggest that IRGM proteins indirectly modulate the localization of GBPs through a distinct mechanism from that through which they regulate IRG protein localization. Further, these results suggest that a core function of IRGM proteins is to regulate autophagic flux, which influences the localization of GBPs and possibly other factors that instruct cell-autonomous immune resistance.

Duke Scholars

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

September 2, 2011

Volume

286

Issue

35

Start / End Page

30471 / 30480

Location

United States

Related Subject Headings

  • Ubiquitin
  • Protein Binding
  • Phagosomes
  • Models, Biological
  • Mice, Transgenic
  • Mice
  • Interferons
  • Immunoprecipitation
  • Glycosides
  • Gene Expression Regulation
 

Citation

APA
Chicago
ICMJE
MLA
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Traver, M. K., Henry, S. C., Cantillana, V., Oliver, T., Hunn, J. P., Howard, J. C., … Taylor, G. A. (2011). Immunity-related GTPase M (IRGM) proteins influence the localization of guanylate-binding protein 2 (GBP2) by modulating macroautophagy. J Biol Chem, 286(35), 30471–30480. https://doi.org/10.1074/jbc.M111.251967
Traver, Maria K., Stanley C. Henry, Viviana Cantillana, Tim Oliver, Julia P. Hunn, Jonathan C. Howard, Sandra Beer, Klaus Pfeffer, Jörn Coers, and Gregory A. Taylor. “Immunity-related GTPase M (IRGM) proteins influence the localization of guanylate-binding protein 2 (GBP2) by modulating macroautophagy.J Biol Chem 286, no. 35 (September 2, 2011): 30471–80. https://doi.org/10.1074/jbc.M111.251967.
Traver MK, Henry SC, Cantillana V, Oliver T, Hunn JP, Howard JC, et al. Immunity-related GTPase M (IRGM) proteins influence the localization of guanylate-binding protein 2 (GBP2) by modulating macroautophagy. J Biol Chem. 2011 Sep 2;286(35):30471–80.
Traver, Maria K., et al. “Immunity-related GTPase M (IRGM) proteins influence the localization of guanylate-binding protein 2 (GBP2) by modulating macroautophagy.J Biol Chem, vol. 286, no. 35, Sept. 2011, pp. 30471–80. Pubmed, doi:10.1074/jbc.M111.251967.
Traver MK, Henry SC, Cantillana V, Oliver T, Hunn JP, Howard JC, Beer S, Pfeffer K, Coers J, Taylor GA. Immunity-related GTPase M (IRGM) proteins influence the localization of guanylate-binding protein 2 (GBP2) by modulating macroautophagy. J Biol Chem. 2011 Sep 2;286(35):30471–30480.

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

September 2, 2011

Volume

286

Issue

35

Start / End Page

30471 / 30480

Location

United States

Related Subject Headings

  • Ubiquitin
  • Protein Binding
  • Phagosomes
  • Models, Biological
  • Mice, Transgenic
  • Mice
  • Interferons
  • Immunoprecipitation
  • Glycosides
  • Gene Expression Regulation