Donders Institute for Brain, Cognition and Behaviour, and Nijmegen Centre for Molecular Life Sciences (NCMLS), Department of Molecular Animal Physiology, Radboud University Nijmegen, Geert Grooteplein Zuid 28, 6525 GA Nijmegen, The Netherlands.
Cell Mol Life Sci. 2010 Feb;67(4):629-40. doi: 10.1007/s00018-009-0200-6. Epub 2009 Nov 28.
The vacuolar (H(+))-ATPase (V-ATPase) is the main regulator of intraorganellar pH and in neuroendocrine cells is controlled by its accessory subunit, Ac45. Here, we report the discovery of the first isoform of a V-ATPase accessory subunit, namely an Ac45-like protein, denoted Ac45LP. Phylogenetic analysis revealed a lineage-dependent evolutionary history: Ac45 is absent in birds, and Ac45LP is absent in placental mammals, whereas all other tetrapod species contain both genes. In contrast to Ac45, Ac45LP is not proteolytically cleaved, a prerequisite for proper Ac45 routing. Intriguingly, Xenopus Ac45LP mRNA was expressed in developing neural tissue and in neural crest cells. In adult Xenopus, Ac45 mRNA is widely expressed mostly in neuroendocrine tissues, while Ac45LP mRNA expression was found to be restricted to the kidney and the lung. This novel Ac45LP may provide additional possibilities for V-ATPase regulation during neurodevelopment as well as in kidney and lung cells.
液泡（H(+））-ATP 酶（V-ATPase）是细胞器内 pH 值的主要调节剂，在神经内分泌细胞中受其辅助亚基 Ac45 控制。在这里，我们报告了第一个 V-ATPase 辅助亚基同工型的发现，即 Ac45 样蛋白，称为 Ac45LP。系统发育分析显示出与谱系相关的进化历史：鸟类中缺少 Ac45，胎盘哺乳动物中缺少 Ac45LP，而所有其他四足动物物种都含有这两个基因。与 Ac45 不同，Ac45LP 不会被蛋白水解切割，这是 Ac45 正确路由的先决条件。有趣的是，非洲爪蟾 Ac45LP mRNA 在发育中的神经组织和神经嵴细胞中表达。在成年非洲爪蟾中，Ac45 mRNA 广泛表达于大多数神经内分泌组织，而 Ac45LP mRNA 的表达仅限于肾脏和肺部。这种新型的 Ac45LP 可能为神经发育以及肾脏和肺部细胞中的 V-ATPase 调节提供了额外的可能性。
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