Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Biochem J. 2011 Oct 15;439(2):249-55. doi: 10.1042/BJ20110759.
LAT2 (system L amino acid transporter 2) is composed of the subunits Slc7a8/Lat2 and Slc3a2/4F2hc. This transporter is highly expressed along the basolateral membranes of absorptive epithelia in kidney and small intestine, but is also abundant in the brain. Lat2 is an energy-independent exchanger of neutral amino acids, and was shown to transport thyroid hormones. We report in the present paper that targeted inactivation of Slc7a8 leads to increased urinary loss of small neutral amino acids. Development and growth of Slc7a8(-/-) mice appears normal, suggesting functional compensation of neutral amino acid transport by alternative transporters in kidney, intestine and placenta. Movement co-ordination is slightly impaired in mutant mice, although cerebellar development and structure remained inconspicuous. Circulating thyroid hormones, thyrotropin and thyroid hormone-responsive genes remained unchanged in Slc7a8(-/-) mice, possibly because of functional compensation by the thyroid hormone transporter Mct8 (monocarboxylate transporter 8), which is co-expressed in many cell types. The reason for the mild neurological phenotype remains unresolved.
LAT2（系统 L 氨基酸转运体 2）由 Slc7a8/Lat2 和 Slc3a2/4F2hc 亚基组成。这种转运体在肾脏和小肠的吸收上皮的基底外侧膜上高度表达，但在大脑中也很丰富。Lat2 是一种不依赖能量的中性氨基酸交换体，被证明可以转运甲状腺激素。本研究报道，Slc7a8 的靶向失活导致尿中小中性氨基酸的丢失增加。Slc7a8(-/-) 小鼠的发育和生长似乎正常，这表明肾脏、肠道和胎盘中的替代转运体对中性氨基酸转运具有功能代偿作用。突变小鼠的运动协调性略有受损，尽管小脑的发育和结构仍不明显。Slc7a8(-/-) 小鼠中循环甲状腺激素、促甲状腺素和甲状腺激素反应基因没有变化，可能是由于多细胞表达的甲状腺激素转运体 Mct8（单羧酸转运体 8）的功能代偿。轻度神经表型的原因仍未解决。
