From the Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
the Department of Otolaryngology-Head and Neck Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611.
J Biol Chem. 2018 Jun 29;293(26):9970-9980. doi: 10.1074/jbc.RA118.001831. Epub 2018 May 18.
Pendrin and prestin belong to the solute carrier 26 (SLC26) family of anion transporters. Prestin is unique among the SLC26 family members in that it displays voltage-driven motor activity (electromotility) and concurrent gating currents that manifest as nonlinear cell membrane electrical capacitance (nonlinear capacitance (NLC)). Although the anion transport mechanism of the SLC26 proteins has begun to be elucidated, the molecular mechanism of electromotility, which is thought to have evolved from an ancestral ion transport mechanism, still remains largely elusive. Here, we demonstrate that pendrin also exhibits large NLC and that charged residues present in one of the extracellular loops of pendrin and prestin play significant roles in setting the voltage-operating points of NLC. Our results suggest that the molecular mechanism responsible for sensing voltage is not unique to prestin among the members of the SLC26 family and that this voltage-sensing mechanism works independently of the anion transport mechanism.
Pendrin 和 prestin 属于溶质载体 26（SLC26）家族的阴离子转运体。与 SLC26 家族的其他成员不同， prestin 具有电压驱动的马达活性（电动性）和并发的门控电流，表现为非线性细胞膜电电容（非线性电容（NLC））。尽管 SLC26 蛋白的阴离子转运机制已经开始阐明，但被认为是从祖先的离子转运机制进化而来的电动性的分子机制仍然很大程度上难以捉摸。在这里，我们证明 pendrin 也表现出大的 NLC，并且 pendrin 和 prestin 之一的细胞外环中的带电残基在设定 NLC 的电压操作点方面起着重要作用。我们的结果表明，负责感应电压的分子机制在 SLC26 家族成员中并非 prestin 所特有，并且这种电压感应机制独立于阴离子转运机制。
