美国休斯顿贝勒医学院科研团队近日取得一项新成果。经过不懈努力，他们报道了脑甲状腺激素通过MCT8和OATP1C1转运的结构研究。相关论文发表在2025年7月17日出版的《细胞》杂志上。

研究团队报道了MCT8和OATP1C1与活性甲状腺激素三碘甲状腺原氨酸（T3）和原激素甲状腺素（T4）在2.9和2.3 分别的决议。结合功能研究，该研究组阐明了它们独特的甲状腺激素识别和转运机制，并解释了疾病突变。虽然细胞外变构位点不是SLC转运体的共同特征，但研究小组在OATP1C1中发现了一个。总的来说，这些发现阐明了甲状腺激素运输的关键方面，这是发育和疾病的基本过程。

据介绍，充足的甲状腺激素输送到大脑对正常的神经发育至关重要。MCT8和OATP1C1是两种溶质载体（SLC）转运蛋白，介导甲状腺激素通过血脑屏障进入中枢神经系统。MCT8突变可导致Allan-Herndon-Dudley综合征（AHDS），这是一种以神经发育障碍和周围性甲状腺功能亢进为特征的x系出生缺陷，而OATP1C1缺乏与脑代谢低下和进行性神经退行性变有关。

附：英文原文

Title: Structural insights into brain thyroid hormone transport via MCT8 and OATP1C1

Author: Yunhui Ge, Tongyi Dou, Thu Uyen Nguyen, Gaya P. Yadav, Theodore G. Wensel, Jiansen Jiang, Pengxiang Huang

Issue&Volume: 2025-07-17

Abstract: Adequate delivery of thyroid hormones to the brain is crucial for normal neurological development. MCT8 and OATP1C1, two solute carrier (SLC) transporters, mediate the passage of thyroid hormones across the blood-brain barrier and into the central nervous system. Mutations in MCT8 result in Allan-Herndon-Dudley syndrome (AHDS), an X-linked birth defect characterized by neurodevelopmental impairments and peripheral hyperthyroidism, whereas OATP1C1 deficiency is linked to brain hypometabolism and progressive neurodegeneration. Here, we report cryoelectron microscopy (cryo-EM) structures of MCT8 and OATP1C1 bound with the active thyroid hormone triiodothyronine (T3) and the prohormone thyroxine (T4) at 2.9 and 2.3 resolutions, respectively. Combined with functional studies, we elucidate their distinct thyroid hormone recognition and transport mechanisms and explain disease mutations. Although extracellular allosteric sites are not a common feature of SLC transporters, we identify one in OATP1C1. Collectively, these findings illuminate key aspects of thyroid hormone transport, a fundamental process in development and disease.

DOI: 10.1016/j.cell.2025.06.032

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00734-2