Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
PLoS One. 2012;7(6):e39881. doi: 10.1371/journal.pone.0039881. Epub 2012 Jun 22.
The regulation of the acid-base balance in cells is essential for proper cellular homeostasis. Disturbed acid-base balance directly affects cellular physiology, which often results in various pathological conditions. In every living organism, the protein family of carbonic anhydrases regulate a broad variety of homeostatic processes. Here we describe the identification, mapping and cloning of a zebrafish carbonic anhydrase 5 (ca5) mutation, collapse of fins (cof), which causes initially a collapse of the medial fins followed by necrosis and rapid degeneration of the embryo. These phenotypical characteristics can be mimicked in wild-type embryos by acetazolamide treatment, suggesting that CA5 activity in zebrafish is essential for a proper development. In addition we show that CA5 regulates acid-base balance during embryonic development, since lowering the pH can compensate for the loss of CA5 activity. Identification of selective modulators of CA5 activity could have a major impact on the development of new therapeutics involved in the treatment of a variety of disorders.
细胞酸碱平衡的调节对细胞的内稳态至关重要。酸碱平衡紊乱会直接影响细胞的生理机能，常常导致各种病理状况的发生。在所有生物体中，碳酸酐酶家族的蛋白调节着广泛的内稳态过程。在这里，我们描述了斑马鱼碳酸酐酶 5（ca5）突变体 collapse of fins（cof）的鉴定、定位和克隆，该突变导致中鳍最初的坍塌，随后是胚胎的坏死和快速退化。在野生型胚胎中，通过乙酰唑胺处理可以模拟出这些表型特征，这表明 CA5 在斑马鱼的正常发育中是必需的。此外，我们还表明 CA5 在胚胎发育过程中调节酸碱平衡，因为降低 pH 值可以补偿 CA5 活性的丧失。鉴定 CA5 活性的选择性调节剂可能会对开发涉及治疗多种疾病的新疗法产生重大影响。
