NDLI: Palmitoylation of the Immunity Related GTPase, Irgm1: Impact on Membrane Localization and Ability to Promote Mitochondrial Fission

Content Provider	PubMed Central
Author	Henry, Stanley C. Schmidt, Elyse A. Fessler, Michael B. Taylor, Gregory A.
Editor	Goot, F. Gisou Van Der
Copyright Year	2014
Abstract	The Immunity-Related GTPases (IRG) are a family of large GTPases that mediate innate immune responses. Irgm1 is particularly critical for immunity to bacteria and protozoa, and for inflammatory homeostasis in the intestine. Although precise functions for Irgm1 have not been identified, prior studies have suggested roles in autophagy/mitophagy, phagosome remodeling, cell motility, and regulating the activity of other IRG proteins. These functions ostensibly hinge on the ability of Irgm1 to localize to intracellular membranes, such as those of the Golgi apparatus and mitochondria. Previously, it has been shown that an amphipathic helix, the αK helix, in the C-terminal portion of the protein partially mediates membrane binding. However, in absence of αK, there is still substantial binding of Irgm1 to cellular membranes, suggesting the presence of other membrane binding motifs. In the current work, an additional membrane localization motif was found in the form of palmitoylation at a cluster of cysteines near the αK. An Irgm1 mutant possessing alanine to cysteine substitutions at these amino acids demonstrated little residual palmitoylation, yet it displayed only a small decrease in localization to the Golgi and mitochondria. In contrast, a mutant containing the palmitoylation mutations in combination with mutations disrupting the amphipathic character of the αK displayed a complete loss of apparent localization to the Golgi and mitochondria, as well as an overall loss of association with cellular membranes in general. Additionally, Irgm1 was found to promote mitochondrial fission, and this function was undermined in Irgm1 mutants lacking the palmitoylation domain, and to a greater extent in those lacking the αK, or the αK and palmitoylation domains combined. Our data suggest that palmitoylation together with the αK helix firmly anchor Irgm1 in the Golgi and mitochondria, thus facilitating function of the protein.
Related Links	http://dx.doi.org/10.1371/journal.pone.0095021
Starting Page	95021
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	4
Volume Number	9
Language	English
Publisher	Public Library of Science
Publisher Date	2014-04-21
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Interferon-inducible Immunity-Related GTPase Irgm1 regulates IFN-γ-dependent host defense, lymphocyte survival and autophagy

Localisation and Mislocalisation of the Interferon-Inducible Immunity-Related GTPase, Irgm1 (LRG-47) in Mouse Cells

The dynamin-related GTPase Dnm1 regulates mitochondrial fission in yeast

Discovery of the membrane receptor for mitochondrial fission GTPase Drp1

Immunity Related GTPase Irgm1 promotes expansion of activated CD4+ T cell populations by preventing interferon-γ-induced cell death

Metabolic Alterations Contribute to Enhanced Inflammatory Cytokine Production in Irgm1-deficient Macrophages

Dynamin-related Protein 1 Oligomerization in Solution Impairs Functional Interactions with Membrane-anchored Mitochondrial Fission Factor

Loss of the interferon-γ-inducible regulatory immunity-related GTPase (IRG), Irgm1, causes activation of effector IRG proteins on lysosomes, damaging lysosomal function and predicting the dramatic susceptibility of Irgm1-deficient mice to infection

Palmitoylation-dependent Membrane Localization of the Rice Resistance Protein Pit Is Critical for the Activation of the Small GTPase OsRac1

Palmitoylation of the Immunity Related GTPase, Irgm1: Impact on Membrane Localization and Ability to Promote Mitochondrial Fission

Similar Documents

Interferon-inducible Immunity-Related GTPase Irgm1 regulates IFN-γ-dependent host defense, lymphocyte survival and autophagy

Localisation and Mislocalisation of the Interferon-Inducible Immunity-Related GTPase, Irgm1 (LRG-47) in Mouse Cells

The dynamin-related GTPase Dnm1 regulates mitochondrial fission in yeast

Discovery of the membrane receptor for mitochondrial fission GTPase Drp1

Immunity Related GTPase Irgm1 promotes expansion of activated CD4+ T cell populations by preventing interferon-γ-induced cell death

Metabolic Alterations Contribute to Enhanced Inflammatory Cytokine Production in Irgm1-deficient Macrophages

Dynamin-related Protein 1 Oligomerization in Solution Impairs Functional Interactions with Membrane-anchored Mitochondrial Fission Factor

Loss of the interferon-γ-inducible regulatory immunity-related GTPase (IRG), Irgm1, causes activation of effector IRG proteins on lysosomes, damaging lysosomal function and predicting the dramatic susceptibility of Irgm1-deficient mice to infection

Palmitoylation-dependent Membrane Localization of the Rice Resistance Protein Pit Is Critical for the Activation of the Small GTPase OsRac1

Palmitoylation of the Immunity Related GTPase, Irgm1: Impact on Membrane Localization and Ability to Promote Mitochondrial Fission