生物
单倍型
免疫印迹
分子生物学
基因亚型
流式细胞术
基因
红细胞
质膜Ca2+ATPase
单核苷酸多态性
基因表达
遗传学
生物化学
ATP酶
等位基因
基因型
酶
作者
Boglárka Zámbó,György Várady,Rita Padányi,Edit Szabó,Á. Németh,Tamás Langó,Ágnes Enyedi,Balázs Sarkadi
出处
期刊:Cell Calcium
[Elsevier]
日期:2017-07-01
卷期号:65: 73-79
被引量:30
标识
DOI:10.1016/j.ceca.2017.02.001
摘要
Plasma membrane Ca2+-ATPases are key calcium exporter proteins in most tissues, and PMCA4b is the main calcium transporter in the human red blood cells (RBCs). In order to assess the expression level of PMCA4b, we have developed a flow cytometry and specific antibody binding method to quantitatively detect this protein in the erythrocyte membrane. Interestingly, we found several healthy volunteers showing significantly reduced expression of RBC-PMCA4b. Western blot analysis of isolated RBC membranes confirmed this observation, and indicated that there are no compensatory alterations in other PMCA isoforms. In addition, reduced PMCA4b levels correlated with a lower calcium extrusion capacity in these erythrocytes. When exploring the potential genetic background of the reduced PMCA4b levels, we found no missense mutations in the ATP2B4 coding regions, while a formerly unrecognized minor haplotype in the predicted second promoter region closely correlated with lower erythrocyte PMCA4b protein levels. In recent GWA studies, SNPs in this ATP2B4 haplotype have been linked to reduced mean corpuscular hemoglobin concentrations (MCHC), and to protection against malaria infection. Our data suggest that an altered regulation of gene expression is responsible for the reduced RBC-PMCA4b levels that is probably linked to the development of human disease-related phenotypes.
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