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Wong VW, Saunders AE, Hutchings A, et al. The autoimmunity-related GIMAP5 GTPase is a lysosome-associated protein. Self Nonself. 2010;1(3):259-268doi: 10.4161/self.1.3.12819.
Wong, V. W., Saunders, A. E., Hutchings, A., Pascall, J. C., Carter, C., Bright, N. A., Walker, S. A., Ktistakis, N. T., & Butcher, G. W. (2010). The autoimmunity-related GIMAP5 GTPase is a lysosome-associated protein. Self/nonself, 1(3), 259-268. https://doi.org/10.4161/self.1.3.12819
Wong, Vivian Wy, et al. "The autoimmunity-related GIMAP5 GTPase is a lysosome-associated protein." Self/nonself vol. 1,3 (2010): 259-268. doi: https://doi.org/10.4161/self.1.3.12819
Wong VW, Saunders AE, Hutchings A, Pascall JC, Carter C, Bright NA, Walker SA, Ktistakis NT, Butcher GW. The autoimmunity-related GIMAP5 GTPase is a lysosome-associated protein. Self Nonself. 2010 Jul;1(3):259-268. doi: 10.4161/self.1.3.12819. Epub 2010 Jun 25. PMID: 21487483; PMCID: PMC3047789.
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Self Nonself. 2010 Jul;1(3):259-268. doi: 10.4161/self.1.3.12819. Epub 2010 Jun 25.

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

Self/nonself

Vivian Wy Wong, Amy E Saunders, Amanda Hutchings, John C Pascall, Christine Carter, Nicholas A Bright, Simon A Walker, Nicholas T Ktistakis, Geoffrey W Butcher

Affiliations

  1. Immunology Programme, The Babraham Institute, Cambridge, UK.

PMID: 21487483 PMCID: PMC3047789 DOI: 10.4161/self.1.3.12819

Abstract

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.

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