Characterization of a murine high-affinity thiamine transporter, Slc19a2
Characterization of a murine high-affinity thiamine transporter, Slc19a2
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DOI：
10.1006/mgme.2001.3241
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发表时间：
2001-09-01
影响因子：
3.8
通讯作者：
Neufeld, EJ
中科院分区：
文献类型：
--
作者：
Fleming, JC;Steinkamp, MP;Neufeld, EJ
硫胺素反应性巨幼细胞性贫血伴耳聋和糖尿病 (TRMA) 是一种罕见的常染色体隐性遗传硫胺素转运疾病。先前的研究表明，这种疾病是由编码高亲和力硫胺素转运蛋白的SLC19A2基因突变引起的。我们假设由 SLC19A2 介导的硫胺素转运在多个器官系统的发育和/或维持中发挥作用，特别是红细胞生成系统、听觉系统和葡萄糖稳态系统。为了进一步研究转运蛋白，我们克隆了小鼠 Slc19a2 基因座并表征了所得蛋白质。鼠 Slc19a2 是一种 498 个氨基酸的蛋白质，具有 12 个预测的跨膜结构域。该基因跨度约为 13kb，有 6 个外显子，结构与人类同源基因相同。我们将 Slc19a2 基因定位于小鼠 1 号染色体，该区域与包含 TRMA 基因座的人类染色体 1q23 同线性。 HEK293T 细胞中 Slc19a2 的瞬时表达导致 [H-3] 硫胺素的特异性摄取，证实了硫胺素转运蛋白的功能。小鼠组织的蛋白质印迹分析揭示了 Slc19a2 蛋白的广泛分布。免疫组织化学研究表明，Slc19a2 在细胞表面和细胞内表达，并且特异性定位于耳蜗、小肠和胰腺的细胞亚群。 (C) 2001 年学术出版社。
Thiamine-responsive megaloblastic anemia with deafness and diabetes (TRMA) is a rare autosomal recessive disorder of thiamine transport. Previous studies have demonstrated that the disease is caused by mutations in the SLC19A2 gene encoding a high-affinity thiamine transporter. We hypothesize that thiamine transport, mediated by SLC19A2, plays a role in the development and or maintenance of several organ systems, in particular the erythropoietic, auditory, and glucose homeostasis systems. To investigate the transporter further, we cloned the murine Slc19a2 locus and characterized the resulting protein. Murine Slc19a2 is a 498 amino acid protein, with 12 predicted transmembrane domains. The gene spans similar to 13kb with 6 exons, structurally identical to that of the human homolog. We localized the Slc19a2 gene to mouse chromosome 1, a region syntenic to human chromosome 1q23 that contains the TRMA locus. Transient expression of Slc19a2 in HEK293T cells resulted in specific uptake of [H-3] thiamine, confirming a thiamine transporter function. Western blot analysis of mouse tissues reveals a wide distribution of Slc19a2 protein. Immunohistochemistry studies indicate that Slc19a2 is expressed on the cell surface and intracellularly, and is specifically localized to a subpopulation of cells in cochlea, small intestine, and pancreas. (C) 2001 Academic Press.