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Translocator protein 2 (TSPO2), a new family of proteins involved in cholesterol redistribution in erythropoiesis
Author(s) -
Fan Jinjiang,
Papadopoulos Vassilios
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.521.1
Subject(s) - translocator protein , erythropoiesis , biology , gene , ectopic expression , microbiology and biotechnology , saccharomyces cerevisiae , biochemistry , medicine , anemia , neuroinflammation , immunology , inflammation
Translocator protein (18‐kDa; TSPO) is a highly conserved cholesterol‐ and drug‐binding protein. Analysis of Tspo ‐like sequences from different organisms revealed the presence of evolutionary conserved genes which arose by gene duplications before the divergence of avians and mammals. This new family of genes was named Tspo2 and found to be under strong purifying selection, suggesting that it serves a conserved biological function. The predicted cholesterol‐binding motif at the C‐terminus of TSPO was present in TSPO2, suggesting a role in cholesterol trafficking and/or targeting. In contrast to the mitochondrial TSPO, TSPO2 was found in nuclear and ER membranes. Heterologous expression of TSPO2 in Saccharomyces cerevisiae demonstrated that TSPO2 indeed binds cholesterol with high affinity. However, TSPO2 lost the TSPO drug binding ability. Spatial and temporal distribution of Tspo2 mRNA in the mouse demonstrated its presence in hematopoetic tissues and expression in an erythroid cell type‐specific manner. Overexpression of Tspo2 in erythroid cells resulted in the redistribution of the intracellular free cholesterol which has been linked to the expulsion of the nucleus from erythroblasts leading to erythrocyte maturation. These data suggest that the identified gene expansion in Tspo family supports a specialized function of the TSPO2 in erythropoiesis of endothermic animals, including humans.