Requirement of Prorenin Receptor and Vacuolar H+-ATPase-Mediated Acidification for Wnt Signaling
Requirement of Prorenin Receptor and Vacuolar H+-ATPase-Mediated Acidification for Wnt Signaling
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DOI：
10.1126/science.1179802
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发表时间：
2010-01-22
期刊：
影响因子：
56.9
通讯作者：
Niehrs, Christof
中科院分区：
文献类型：
--
作者：
Cruciat, Cristina-Maria;Ohkawara, Bisei;Niehrs, Christof
WNT/β-catenin信号在干细胞生物学、胚胎发育和包括癌症在内的疾病中都很重要。然而，Wnt信号传递的机制，特别是受体是如何被激活的，仍然不完全清楚。我们发现原肾素受体(PRR)是Wnt受体复合体的一种成分。PRR作为Wnt受体和空泡H+-三磷酸腺苷酶(V-ATPase)复合体之间的适配器，其功能不依赖于肾素。此外，PRR和V-ATPase在非洲爪哇早期中枢神经系统发育的前后模式过程中还需要介导Wnt信号。结果揭示了原肾素受体、V-ATPase活性和酸化在Wnt/β-catenin信号转导过程中的一个意想不到的作用。
Wnt/beta-catenin signaling is important in stem cell biology, embryonic development, and disease, including cancer. However, the mechanism of Wnt signal transmission, notably how the receptors are activated, remains incompletely understood. We found that the prorenin receptor (PRR) is a component of the Wnt receptor complex. PRR functions in a renin-independent manner as an adaptor between Wnt receptors and the vacuolar H+-adenosine triphosphatase (V-ATPase) complex. Moreover, PRR and V-ATPase were required to mediate Wnt signaling during antero-posterior patterning of Xenopus early central nervous system development. The results reveal an unsuspected role for the prorenin receptor, V-ATPase activity, and acidification during Wnt/beta-catenin signaling.