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Traver, Maria K., Henry, Stanley C., Cantillana, Viviana, Oliver, Tim, Hunn, Julia P., Howard, Jonathan C., Beer, Sandra, Pfeffer, Klaus ORCID: 0000-0002-5652-6330, Coers, Joern and Taylor, Gregory 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). S. 30471 - 30481. BETHESDA: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. ISSN 1083-351X

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Abstract

The immunity-related GTPases (IRGs) are a family of proteins induced by interferon-gamma 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Traver, Maria K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Henry, Stanley C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cantillana, Viviana UNSPECIFIED UNSPECIFIED UNSPECIFIED Oliver, Tim UNSPECIFIED UNSPECIFIED UNSPECIFIED Hunn, Julia P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Howard, Jonathan C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Beer, Sandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfeffer, Klaus UNSPECIFIED orcid.org/0000-0002-5652-6330 UNSPECIFIED Coers, Joern UNSPECIFIED UNSPECIFIED UNSPECIFIED Taylor, Gregory A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-489215
DOI:	10.1074/jbc.M111.251967
Journal or Publication Title:	J. Biol. Chem.
Volume:	286
Number:	35
Page Range:	S. 30471 - 30481
Date:	2011
Publisher:	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Place of Publication:	BETHESDA
ISSN:	1083-351X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INDUCIBLY EXPRESSED GTPASE; AUTOPHAGY-DEFICIENT MICE; P47 RESISTANCE GTPASES; INTERFERON-GAMMA; IFN-GAMMA; HOST-RESISTANCE; TOXOPLASMA-GONDII; CELLULAR-RESPONSE; MYCOBACTERIUM-TUBERCULOSIS; INTRACELLULAR PATHOGENS Multiple languages Biochemistry & Molecular Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48921