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首页> 外文期刊>Cellular Physiology and Biochemistry >Differential localization of vacuolar H+-ATPases containing a1, a2, a3, or a4 (ATP6V0A1-4) subunit isoforms along the nephron
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Differential localization of vacuolar H+-ATPases containing a1, a2, a3, or a4 (ATP6V0A1-4) subunit isoforms along the nephron

机译：沿肾单位包含a1，a2，a3或a4（ATP6V0A1-4）亚基的液泡H + -ATPase的差异定位

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摘要

Vacuolar H+-ATPase are multi-subunit containing pumps important for several processes along the nephron such as receptor mediated endocytosis, acidification of intracellular organelles, bicarbonate reabsorption and secretion, and H+-extrusion. Mutations in the human a4 (ATP6V0A4) subunit cause distal renal tubular acidosis (dRTA). There are 4 known isoforms of the 'a' subunit (a1-a4). Here we investigated the expression and localization of all four isoforms in mouse kidney. Real-time PCR detected mRNAs encoding all four 'a' isoforms in mouse kidney with a relative abundance in the following order: a4 > a2=a1 > a3. Immunolocalization demonstrated expression of all 'a' subunits in the proximal tubule and in the intercalated cells of the collecting system. In intercalated cells a1 and a4 isoforms appeared on both the apical and basolateral side and were expressed in all subtypes of intercalated cells. In contrast, a2, and a3 were only found in the apical membrane. a1 and a4 were colocalized in the same cells with AE1 or pendrin, whereas a2 was only found in AE1 positive cells but absent from pendrin expressing intercalated cells. These results suggest that vacuolar H+-ATPases containing different 'a' isoforms may serve specific and distinct functions and may help explaining why loss of the a4 isoform causes only dRTA without an apparent defect in the proximal tubule.
机译：泡状H + -ATPase是含有多亚基的泵，对于肾单位的多个过程至关重要，例如受体介导的内吞作用，细胞内细胞器的酸化，碳酸氢盐的重吸收和分泌以及H +挤出。人a4（ATP6V0A4）亚基的突变会导致远端肾小管性酸中毒（dRTA）。 “ a”亚基（a1-a4）有4种已知的同工型。在这里，我们研究了小鼠肾脏中所有四种同工型的表达和定位。实时PCR检测到的编码小鼠肾脏中所有四个'a'亚型的mRNA的相对丰度顺序如下：a4> a2 = a1> a3。免疫定位证实了所有“ a”亚基在收集管的近端小管和插入细胞中的表达。在插层细胞中，a1和a4亚型同时出现在顶侧和基底外侧，并在所有亚型的插层细胞中表达。相反，a2和a3仅在顶膜中发现。 a1和a4与AE1或pendrin在同一细胞中共定位，而a2仅在AE1阳性细胞中发现，而表达pendrin的插层细胞却不存在。这些结果表明，含有不同“ a”同工型的液泡H + -ATPase可能具有特定而独特的功能，并且可以帮助解释为什么a4同工型的丢失仅导致dRTA而近端小管无明显缺陷。

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