Discovery of voltage-sensing ability in pendrin, an anion transporter
Overview of the press release
Pendrin (SLC26A4) and prestin (SLC26A5) belong to the SLC26 anion transporter family and play essential roles in mammalian hearing. Although their amino acid sequences show high similarity, their physiological functions are distinct: similar to most other members of the SLC26 family, pendrin exchanges anions across plasma membrane, while prestin acts as a voltage-driven molecular motor and amplifies sound signals in the inner ear by changing the length of the outer hair cells. The voltage-sensing ability, which is a basis for the voltage-driven motility, has been presumed to be equipped only in prestin among the SLC26 family.
In the present study, however, a research team led by Assistant Professor Kazuaki Homma (Feinberg School of Medicine, Northwestern University, U.S.A.) and Assistant Professor Tomohiro Shima (Department of Biological Sciences, Graduate School of Science, The University of Tokyo) revealed that prestin and pendrin share a common voltage-sensing mechanism. By using high-precision electrophysiological measurements combined with cellular, chemical, and mutational manipulations, the team demonstrated pendrin’s voltage-sensing ability, which has been long overlooked. Moreover, the team found that the characteristic extracellular loop of both proteins modulates their voltage-sensing properties.
This study provides crucial information on how the two proteins adopt different functions. Furthermore, the method used to modulate the voltage-sensing property will facilitate future development of prestin-based mechano-electro converters, which could theoretically enhance the conversion efficacy ~10,000 times higher than the conventional man-made piezoelectric devices.
Figure: The electrophysiological activities of prestin and pendrin
Structural models of the two proteins (left panels) show the existence of the characteristic extracellular loop (darkened portion) in both proteins. The high-precision electrophysiological measurement demonstrates the bell-shaped membrane potential-capacitance curves (middle panels), suggesting the voltage-sensing ability of these proteins. The research team showed that the voltage-sensing property can be modulated by changing the charge of the extracellular loop (right panels).
Journal Journal of Biological Chemistry Title The extracellular loop of pendrin and prestin modulates their voltage-sensing property Authors Makoto F. Kuwabara, Koichiro Wasano, Satoe Takahashi, Justin Bodner, Tomotaka, Komori, Sotaro Uemura, Jing Zheng, Tomohiro Shima, Kazuaki Homma DOI 10.1074/jbc.RA118.001831 Paper link http://www.jbc.org/content/early/2018/05/18/jbc.RA118.001831
※This publication was last updated on June 29, 2018
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