کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2200753 | 1099969 | 2012 | 10 صفحه PDF | دانلود رایگان |

NGFI-B (NR4A1, Nur77 or TR3) together with Nurr1 (NR4A2) and NOR-1 (NR4A3) constitute the NR4A subgroup of orphan nuclear receptors. They play critical roles in proliferation, differentiation, survival and apoptosis in different cell types, including neurons, immature T-cells, and different cancer cells. As ligand-independent and constitutively active receptors, the diverse biological activities of NGFI-B, Nurr1 and NOR-1 depend on their levels of expression, post-translational modifications and subcellular localization. Nuclear localization of the NR4A proteins leads to transcriptional activity, whereas NGFI-B and recently also NOR-1 have been shown to induce apoptosis by a more direct mechanism when localized at mitochondria. In the present study we investigated mRNA expression and subcellular translocation of the NR4A proteins during glutamate excitotoxicity in rat cerebellar granule neurons. NGFI-B and Nurr1 mRNA, but not NOR-1 mRNA, were induced by treatments associated with calcium influx, although their regulation seemed to be different. NR4Agfp fusion proteins showed a predominant nuclear localization in untreated cells. After glutamate treatment NGFI-Bgfp translocated to cytosol and mitochondria within a few hours, whereas Nurr1gfp translocation was delayed, and NOR-1gfp mainly stayed in the nucleus. Subcellular targeting of NGFI-B seems to be tightly regulated, as a single mutation of threonine 142 altered NGFI-Bgfp localization. Differences in expression and subcellular translocation of NGFI-B, Nurr1, and NOR-1 may reflect different functions in neurons in glutamate excitotoxicity.
► NR4A proteins can regulate survival and apoptosis, by gene regulation and mitochondrial actions.
► NGFI-B and Nurr1, but not NOR-1, mRNA expression is induced in glutamate excitotoxicity in neurons.
► NGFI-Bgfp translocates to cytoplasm and mitochondria after glutamate treatment.
► Nurr1gfp translocates late and NOR-1gfp does not translocate.
► NGFI-Bgfp subcellular localization can be regulated by a single mutation of threonine 142.
Journal: Neurochemistry International - Volume 61, Issue 1, July 2012, Pages 79–88