Non-essential contribution of LRRC8A to volume regulation

Non-essential contribution of LRRC8A to volume regulation
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DOI:
10.1007/s00424-016-1789-6
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发表时间:
2016-05-01
影响因子:
4.5
通讯作者:
Kunzelmann, Karl
Kunzelmann, Karl
中科院分区:
医学3区
文献类型:
--
作者:
Sirianant, Lalida;Wanitchakool, Podchanart;Kunzelmann, Karl

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体积调节是任何活细胞的基本特性,需要严格控制。虽然已经发现不同类型的K+通道参与细胞体积的调节,但新鉴定的体积调节阴离子通道(VRAC)LRRC 8已被认为是体积调节所必需的。在无偏的全基因组小干扰RNA(siRNA)筛选中,两项独立的研究将LRRC 8A/Swell 1鉴定为VRAC的重要组分,因此对于细胞体积调节是不可或缺的。我们重新分析了LRRC 8A在几种细胞类型和各种条件下对VRAC和调节性容积减少(RVD)的作用。虽然LRRC 8A对VRAC的作用及其对RVD的贡献被证实,但我们发现它对肿胀激活的阴离子电流或细胞体积调节或凋亡细胞收缩不是必需的。LRRC 8A的贡献是可变的,并且很大程度上取决于细胞类型。
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.