Lambie Eric J, Tieu Pamela J, Lebedeva Nadja, Church Diane L, Conradt Barbara
Department of Cell and Developmental Biology, Ludwig-Maximillians-University, Munich, Planegg-Martinsried, Germany.
PLoS One. 2013 Oct 9;8(10):e77202. doi: 10.1371/journal.pone.0077202. eCollection 2013.
In previous work, we found that gain-of-function mutations that hyperactivate GEM-1 (an SLC16A transporter protein) can bypass the requirement for GON-2 (a TRPM channel protein) during the initiation of gonadogenesis in C. elegans. Consequently, we proposed that GEM-1 might function as part of a Mg(2+) uptake pathway that functions in parallel to GON-2. In this study, we report that CATP-6, a C. elegans ortholog of the P5B ATPase, ATP13A2 (PARK9), is necessary for gem-1 gain-of-function mutations to suppress the effects of gon-2 inactivation. One possible explanation for this observation is that GEM-1 serves to activate CATP-6, which then functions as a Mg(2+) transporter. However, we found that overexpression of GEM-1 can alleviate the requirement for CATP-6 activity, suggesting that CATP-6 probably acts as a non-essential upstream positive regulator of GEM-1. Our results are consistent with the notion that P5B ATPases govern intracellular levels of Mg(2+) and/or Mn(2+) by regulating the trafficking of transporters and other proteins associated with the plasma membrane.
在之前的研究中，我们发现功能获得性突变会过度激活GEM-1（一种SLC16A转运蛋白），在秀丽隐杆线虫性腺发育起始过程中，这种突变能够绕过对GON-2（一种TRPM通道蛋白）的需求。因此，我们推测GEM-1可能作为镁离子摄取途径的一部分发挥作用，该途径与GON-2平行发挥功能。在本研究中，我们报告称，CATP-6是P5B型ATP酶ATP13A2（PARK9）在秀丽隐杆线虫中的同源物，对于gem-1功能获得性突变抑制gon-2失活的效应而言是必需的。对此观察结果的一种可能解释是，GEM-1用于激活CATP-6，然后CATP-6作为镁离子转运蛋白发挥作用。然而，我们发现GEM-1的过表达可以减轻对CATP-6活性的需求，这表明CATP-6可能作为GEM-1的非必需上游正向调节因子发挥作用。我们的结果与以下观点一致，即P5B型ATP酶通过调节转运蛋白和其他与质膜相关的蛋白质的运输来控制细胞内镁离子和/或锰离子的水平。
