Putative GTPase GIMAP1 is critical for the development of mature B and T lymphocytes

Saunders, Amy E.; Webb, Louise M. C.; Janas, Michelle L.; Hutchings, Amanda; Pascall, John C.; Carter, Christine; Pugh, Nicholas; Morgan, Geoff; Turner, Martin; Butcher, Geoffrey W.

doi:10.1182/blood-2009-08-237586

Cited by 57 publications

(86 citation statements)

References 45 publications

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“…Of significance to the present discussion, recent work in one of our laboratories has demonstrated that GIMAP1, like GIMAP5, is required for the protection of lymphocytes against cell death. 21 Together these data imply that GIMAP proteins are required in different organelles to provide protection against cell death. A mechanistic explanation of these phenomena will therefore need to encompass events in both (endo)-lysosomes and the Golgi apparatus.…”

Section: Gimap5mentioning

confidence: 95%

The autoimmunity-related GIMAP5 GTPase is a lysosome-associated protein

Wong¹,

Saunders²,

Pascall³

et al. 2010

Self/Nonself

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A mutation in the rat GIMAP5 gene predisposes for autoimmunity, most famously in the BB rat model of autoimmune type 1 diabetes mellitus. This mutation is associated with severe peripheral T lymphopenia, as is mutation of the same gene in mice, but the mechanism by which GIMAP5 normally protects T cells from death is unknown. GIMAP5 is a putative small GTPase, a class of proteins which often fulfil their functions in the vicinity of cellular membranes. The objective of this study was to determine the normal intracellular location of GIMAP5 in lymphoid cells. Combining studies in rat, mouse and human systems, novel monoclonal antibodies (mAbs) were used to examine the localization of GIMAP5 and the closely-related protein, GIMAP1, in lymphoid cells by means of confocal microscopy and sub-cellular fractionation combined with immunoblotting. Additionally, human Jurkat T cells that inducibly express epitope-tagged GIMAP5 were established and used in electron microscopy (EM). Endogenous GIMAP5 was found to be located in a membraneous compartment/s which was also detected by established markers of lysosomes. GIMAP1, by contrast, was found to be located in the Golgi apparatus. EM studies of the inducible Jurkat T cells also found GIMAP5 in lysosomes and, in addition, in multivesicular bodies. This study establishes that the endogenous location of GIMAP5 is in lysosomes and related compartments and provides a clearer context for hypotheses about its mechanism of action. Key words: GIMAP, GTPase, golgi apparatus, lysosome has shown that the mammalian GIMAPs are members of the AIG1 class of GTPases and have relatives in higher plants and non-mammalian vertebrates but not in many convenient experimental organisms such as E. coli, C. elegans or D. melanogaster. The autoimmunity-related GIMAP5 GTPase is a lysosome-associated protein

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Section: Gimap5mentioning

confidence: 95%

The autoimmunity-related GIMAP5 GTPase is a lysosome-associated protein

Wong¹,

Saunders²,

Pascall³

et al. 2010

Self/Nonself

Self Cite

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“…Interestingly, a total of 16 of 39 genomes (41.0%) revealed loss of chromosomal material comprising the EZH2 and GIMAP locus on chromosome 7q36 (supplemental Figure 4). Although this locus and genes in the GIMAP family have been shown to be important in the regulation of T-lymphocyte development and survival, 33,34 they have not been previously implicated in the pathogenesis of T-PLL. Our CNV analysis suggests that the function of these genes is important in regulation of T-cell proliferation and can be deregulated in malignancy.…”

Section: Cnv Analysis Confirms Abnormalities Involving the Atm Locusmentioning

confidence: 99%

Integrated genomic sequencing reveals mutational landscape of T-cell prolymphocytic leukemia

Kiel

Velusamy

Rolland

et al. 2014

Blood

211

212

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“…Mutations in this gene have been linked to susceptibility to recurrent viral infections (36). GIMAP1, GTPase IMAP family member 1, is thought to be involved in the differentiation of inflammatory T helper (Th) cells of the Th1 lineage (37,38). CISH belongs to the cytokine-induced STAT inhibitor (CIS) family, also known as suppressor of cytokine signaling (SOCS) protein family, known to be cytokine-inducible negative regulators of cytokine signaling (39).…”

Section: Microarray Analysis Of Human Nk Cells Stimulated By Gal-9mentioning

confidence: 99%

Galectin-9 Functionally Impairs Natural Killer Cells in Humans and Mice

Golden-Mason

McMahan

Strong³

et al. 2013

J Virol

110

106

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h Galectin-9 is a pleiotropic immune modulator affecting numerous cell types of innate and adaptive immunity. Patients with chronic infection with either hepatitis C virus (HCV) or HIV have elevated circulating levels. Limited data exist on the regulation of natural killer (NK) cell function through interaction with galectin-9. We found that galectin-9 ligation downregulates multiple immune-activating genes, including eight involved in the NK cell-mediated cytotoxicity pathway, impairs lymphokine-activated killing, and decreases the proportion of gamma interferon (IFN-␥)-producing NK cells that had been stimulated with interleukin-12 (IL-12)/IL-15. We demonstrate that the transcriptional and functional changes induced by galectin-9 are independent of Tim-3. Consistent with these results for humans, we find that the genetic absence of galectin-9 in mice is associated with greater IFN-␥ production by NK cells and enhanced degranulation. We also show that in the setting of a short-term (4-day) murine cytomegalovirus infection, terminally differentiated NKs accumulate in the livers of galectin-9 knockout mice, and that hepatic NKs spontaneously produce significantly more IFN-␥ in this setting. Taken together, our results indicate that galectin-9 engagement impairs the function of NK cells, including cytotoxicity and cytokine production.

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Putative GTPase GIMAP1 is critical for the development of mature B and T lymphocytes

Abstract: The guanosine triphosphatases (GTPases) of the immunity-associated protein (GIMAP) family of putative GTPases has been implicated in the regulation of T-lymphocyte development and survival. A mouse conditional knockout allele was generated for the immune GTPase gene

Cited by 57 publications

References 45 publications

The autoimmunity-related GIMAP5 GTPase is a lysosome-associated protein

The autoimmunity-related GIMAP5 GTPase is a lysosome-associated protein

Integrated genomic sequencing reveals mutational landscape of T-cell prolymphocytic leukemia

Galectin-9 Functionally Impairs Natural Killer Cells in Humans and Mice

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