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GTPase of the Immune-Associated Nucleotide Protein 5 Regulates the Lysosomal Calcium Compartment in T Lymphocytes.
- Source :
-
Frontiers in immunology [Front Immunol] 2017 Feb 07; Vol. 8, pp. 94. Date of Electronic Publication: 2017 Feb 07 (Print Publication: 2017). - Publication Year :
- 2017
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Abstract
- T lymphocytes from Gimap5 <superscript>lyp/lyp</superscript> rats carrying a recessive mutation in the GTPase of immune-associated protein 5 ( Gimap5 ) gene undergo spontaneous apoptosis. Molecular mechanisms underlying this survival defect are not yet clear. We have shown that Gimap5 <superscript>lyp/lyp</superscript> T lymphocytes display reduced calcium influx following T cell antigen receptor (TCR) stimulation that was associated with impaired buffering of calcium by mitochondria. Here, we investigated the subcellular localization of GIMAP5 and its influence on Ca <superscript>2+</superscript> response in HEK293T cells and T lymphocytes. The more abundantly expressed GIMAP5v2 localizes to the lysosome and certain endosomal vesicles. Gimap5 <superscript>lyp/lyp</superscript> T lymphocytes showed increased accumulation of calcium in the lysosomes as evidenced by Gly-Phe β-naphthylamide (GPN) triggered Ca <superscript>2+</superscript> release. As a corollary, GPN-induced Ca <superscript>2+</superscript> flux was decreased in HEK293T cells expressing GIMAP5v2. Strikingly, TCR stimulation of rat, mouse, and human T lymphocytes increased lysosomal calcium content. Overall, our findings show that lysosomes modulate cellular Ca <superscript>2+</superscript> response during T cell activation and that GIMAP5 regulates the lysosomal Ca <superscript>2+</superscript> compartment in T lymphocytes.
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 8
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 28223986
- Full Text :
- https://doi.org/10.3389/fimmu.2017.00094