Sirianant Lalida, Wanitchakool Podchanart, Ousingsawat Jiraporn, Benedetto Roberta, Zormpa Anna, Cabrita Ines, Schreiber Rainer, Kunzelmann Karl
Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany.
Pflugers Arch. 2016 May;468(5):805-16. doi: 10.1007/s00424-016-1789-6. Epub 2016 Feb 13.
Volume regulation is an essential property of any living cell and needs to be tightly controlled. While different types of K(+) channels have been found to participate in the regulation of cell volume, the newly identified volume-regulated anion channel (VRAC) LRRC8 has been claimed to be essential for volume regulation. In unbiased genome-wide small interfering RNA (siRNA) screens, two independent studies identified LRRC8A/Swell1 as an essential component of VRAC, thus being indispensable for cellular volume regulation. We reanalyzed the role of LRRC8A for VRAC and regulatory volume decrease (RVD) in several cell types and under various conditions. While the role of LRRC8A for VRAC and its contribution to RVD is confirmed, we find that it is not essential for swelling-activated anion currents or cellular volume regulation, or apoptotic cell shrinkage. The contribution of LRRC8A is variable and largely depending on the cell type.
体积调节是任何活细胞的一项基本特性，需要受到严格控制。虽然已发现不同类型的钾离子通道参与细胞体积调节，但新发现的体积调节性阴离子通道（VRAC）LRRC8被认为对体积调节至关重要。在无偏向的全基因组小干扰RNA（siRNA）筛选中，两项独立研究确定LRRC8A/Swell1是VRAC的一个关键组成部分，因此对于细胞体积调节不可或缺。我们重新分析了LRRC8A在几种细胞类型和各种条件下对VRAC及调节性体积减小（RVD）的作用。虽然LRRC8A对VRAC的作用及其对RVD的贡献得到了证实，但我们发现它对于肿胀激活的阴离子电流、细胞体积调节或凋亡细胞收缩并非必不可少。LRRC8A的贡献是可变的，并且在很大程度上取决于细胞类型。
