Expression of the aspartate/glutamate mitochondrial carriers aralar1 and citrin during development and in adult rat tissues
Expression of the aspartate/glutamate mitochondrial carriers aralar1 and citrin during development and in adult rat tissues
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DOI：
10.1046/j.1432-1033.2002.03018.x
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发表时间：
2002-07-01
期刊：
影响因子：
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通讯作者：
Satrústegui, J
中科院分区：
文献类型：
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作者：
del Arco, A;Morcillo, J;Satrústegui, J
Aralar1 和 citrin 是钙结合线粒体载体亚家族的成员，对应于线粒体天冬氨酸/谷氨酸载体 (AGC) 的两种亚型。这些蛋白质被作用于线粒体内膜外侧的 Ca2+ 激活。尽管已知aralar1主要在骨骼肌、心脏和大脑中表达，而citrin则存在于肝脏、肾脏和心脏中，但这两种蛋白在胚胎和成体组织中的精确组织分布在很大程度上是未知的。我们研究了 aralar1 和 citrin 在小鼠胚胎和成体组织中 mRNA 和蛋白质水平的表达模式。原位杂交分析表明，两种亚型在早期胚胎阶段的鳃弓、皮肌节、四肢和尾芽中都有强烈表达。然而，柠檬酸在这些结构的外胚层成分中更为丰富，而阿拉拉尔则主要定位于间充质。 citrin 在肝脏中的强烈表达是在出生后获得的，而 aralar1 在骨骼肌中的特征性表达是在 E18 时检测到的，而在心脏中的特征性表达在发育早期 (E11) 开始，并且在胚胎晚期优先定位于耳廓心肌。 Aralar1 还在骨髓、T 淋巴细胞和巨噬细胞（包括肝脏中的库普弗细胞）中表达，表明这是造血系统中存在的主要 AGC 亚型。 aralar1 和 citrin 均在胎儿肠道和成人胃、卵巢、睾丸和胰腺中表达，但只有 aralar1 在肺和胰岛素分泌 β 细胞中富集。这些结果表明，aralar1 在比最初认为的更多的组织中表达，并且在肝细胞中不存在，其中 citrin 是唯一存在的 AGC 同工型。这解释了为什么人类的柠檬酸缺乏症（II 型瓜氨酸血症）仅影响肝脏，并表明 aralar1 可以补偿其他组织中柠檬酸的缺乏。
Aralar1 and citrin are members of the subfamily of calcium-binding mitochondrial carriers and correspond to two isoforms of the mitochondrial aspartate/glutamate carrier (AGC). These proteins are activated by Ca2+ acting on the external side of the inner mitochondrial membrane. Although it is known that aralar1 is expressed mainly in skeletal muscle, heart and brain, whereas citrin is present in liver, kidney and heart, the precise tissue distribution of the two proteins in embryonic and adult tissues is largely unknown. We investigated the pattern of expression of aralar1 and citrin in murine embryonic and adult tissues at the mRNA and protein levels. In situ hybridization analysis indicates that both isoforms are expressed strongly in the branchial arches, dermomyotome, limb and tail buds at early embryonic stages. However, citrin was more abundant in the ectodermal components of these structures whereas aralarl had a predominantly mesenchymal localization. The strong expression of citrin in the liver was acquired postnatally, whereas the characteristic expression of aralar1 in skeletal muscle was detected at E18 and that in the heart began early in development (E11) and was preferentially localized to auricular myocardium in late embryonic stages. Aralar1 was also expressed in bone marrow, T-lymphocytes and macrophages, including Kupffer cells in the liver, indicating that this is the major AGC isoform present in the hematopoietic system. Both aralar1 and citrin were expressed in fetal gut and adult stomach, ovary, testis, and pancreas, but only aralar1 is enriched in lung and insulin-secreting beta cells. These results show that aralar1 is expressed in many more tissues than originally believed and is absent from hepatocytes, where citrin is the only AGC isoform present. This explains why citrin deficiency in humans (type II citrullinemia) only affects the liver and suggests that aralar1 may compensate for the lack of citrin in other tissues.