Department of Organismal Animal Physiology, Institute for Water and Wetland Research, Faculty of Science, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.
Endocrinology. 2011 Dec;152(12):5065-73. doi: 10.1210/en.2011-1166. Epub 2011 Sep 27.
Most components of the thyroid system in bony fish have been described and characterized, with the notable exception of thyroid hormone membrane transporters. We have cloned, sequenced, and expressed the zebrafish solute carrier Slc16a2 (also named monocarboxylate transporter Mct8) cDNA and established its role as a thyroid hormone transport protein. The cloned cDNA shares 56-57% homology with its mammalian orthologs. The 526-amino-acid sequence contains 12 predicted transmembrane domains. An intracellular N-terminal PEST domain, thought to be involved in proteolytic processing of the protein, is present in the zebrafish sequence. Measured at initial rate and at the body/rearing temperature of zebrafish (26 C), T(3) uptake by zebrafish Slc16a2 is a saturable process with a calculated Michaelis-Menten constant of 0.8 μM T(3). The rate of T(3) uptake is temperature dependent and Na(+) independent. Interestingly, at 26 C, zebrafish Slc16a2 does not transport T(4). This implies that at a normal body temperature in zebrafish, Slc16a2 protein is predominantly involved in T(3) uptake. When measured at 37 C, zebrafish Slc16a2 transports T(4) in a Na(+)-independent manner. In adult zebrafish, the Slc16a2 gene is highly expressed in brain, gills, pancreas, liver, pituitary, heart, kidney, and gut. Beginning from the midblastula stage, Slc16a2 is also expressed during zebrafish early development, the highest expression levels occurring 48 h after fertilization. This is the first direct evidence for thyroid hormone membrane transporters in fish. We suggest that Slc16a2 plays a key role in the local availability of T(3) in adult tissues as well as during the completion of morphogenesis of primary organ systems.
大多数硬骨鱼类甲状腺系统的组成部分已经被描述和表征，只有甲状腺激素膜转运蛋白除外。我们已经克隆、测序并表达了斑马鱼溶质载体 Slc16a2（也称为单羧酸转运蛋白 Mct8）的 cDNA，并确定了它作为甲状腺激素转运蛋白的作用。克隆的 cDNA 与哺乳动物的同源物有 56-57%的同源性。526 个氨基酸序列包含 12 个预测的跨膜结构域。一个存在于斑马鱼序列中的细胞内 N 端 PEST 结构域，被认为参与了蛋白质的蛋白水解加工。在初始速率和斑马鱼的体温/养殖温度（26°C）下测量时，T3 摄取由斑马鱼 Slc16a2 是一个饱和过程，计算出的米氏常数为 0.8μM T3。T3 的摄取速率与温度有关，与 Na+无关。有趣的是，在 26°C 时，斑马鱼 Slc16a2 不转运 T4。这意味着在斑马鱼的正常体温下，Slc16a2 蛋白主要参与 T3 的摄取。当在 37°C 下测量时，斑马鱼 Slc16a2 以 Na+独立的方式转运 T4。在成年斑马鱼中，Slc16a2 基因在大脑、鳃、胰腺、肝脏、垂体、心脏、肾脏和肠道中高度表达。从中胚层期开始，Slc16a2 在斑马鱼的早期发育过程中也有表达，受精后 48 小时表达水平最高。这是鱼类甲状腺激素膜转运蛋白的第一个直接证据。我们认为 Slc16a2 在成年组织中 T3 的局部可用性以及主要器官系统形态发生完成过程中发挥关键作用。
