The (pro)renin receptor and cardiovascular disease

肾素（原）受体与心血管疾病

• 批准号: 83289788
• 负责人: Professor Dr. Michael Bader
• 金额: --
• 依托单位: Max-Delbrück-Centrum für Molekulare Medizin (MDC) in der Helmholtz-Gemeinschaft
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2013-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/83289788?language=en
• 关键词: pro; renin; receptor; cardiovascular; disease

The (pro)renin receptor (PRR) was initially believed to be a contributor to the pathogenesis of cardiovascular diseases via its involvement in the renin-angiotensin system (RAS). However, a recent paradigm shift suggests a new role for PRR, separate from the RAS, in contributing to cellular homeostasis. Specifically, PRR is thought to be essential for vacuolar H+-ATPase (V-ATPase) activity, and to act as an adaptor between the V-ATPase and the Wnt signalling pathway. Recent PRR conditional knockout studies have confirmed the link between V-ATPase and PRR, with deletion resulting in the accumulation of autophagic vacuoles and animal lethality. Additionally, cleavage by furin at a single site within full-length PRR results in the production of a soluble form of the receptor (sPRR), which is detectable in plasma. Soluble PRR is hypothesised to bind to specific ligands and receptors and mediate signal transduction pathways. The mechanism by which full-length PRR contributes to V-ATPase activity and signal transduction, and the role of sPRR in signal transduction remains unclear. We will determine the molecular details by which PRR contributes to V-ATPase activity, signal transduction and membrane receptor trafficking with a combination of biochemical, cell biology and transgenic animal approaches. Overall, the information generated from this project will reveal the role of PRR in cellular biology and disease.

肾素（原）受体（PRR）最初被认为通过参与肾素-血管紧张素系统（RAS）而导致心血管疾病的发病机制。然而，最近的范式转变表明，PRR 与 RAS 分开，在促进细胞稳态方面发挥着新作用。具体来说，PRR 被认为对于液泡 H+-ATP 酶 (V-ATP 酶) 活性至关重要，并充当 V-ATP 酶和 Wnt 信号通路之间的衔接子。最近的 PRR 条件敲除研究证实了 V-ATPase 和 PRR 之间的联系，敲除会导致自噬泡的积累和动物致死。此外，弗林蛋白酶在全长 PRR 内的单个位点进行切割会导致产生可溶形式的受体 (sPRR)，该受体可在血浆中检测到。假设可溶性 PRR 与特定配体和受体结合并介导信号转导途径。全长 PRR 促进 V-ATP 酶活性和信号转导的机制以及 sPRR 在信号转导中的作用仍不清楚。我们将结合生化、细胞生物学和转基因动物方法，确定 PRR 促进 V-ATP 酶活性、信号转导和膜受体运输的分子细节。总体而言，该项目产生的信息将揭示 PRR 在细胞生物学和疾病中的作用。