Distribution and oligomeric association of splice forms of Na+-K+-ATPase regulatory γ-subunit in rat kidney

Distribution and oligomeric association of splice forms of Na+-K+-ATPase regulatory γ-subunit in rat kidney
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DOI:
10.1152/ajprenal.00146.2001
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发表时间:
2002-03-01
影响因子:
4.2
通讯作者:
Sweadner, KJ
Sweadner, KJ
中科院分区:
医学2区
文献类型:
--
作者:
Arystarkhova, E;Wetzel, RK;Sweadner, KJ

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肾脏Na+-K+-ATP酶与γ亚基(FXYD 2)相关,后者是一种单跨膜蛋白,可改变ATP酶特性。存在两种具有不同氨基末端的剪接变体,γ(a)和γ(B)。两者均位于粗的升支外髓质的内条。相互之间以及α-亚基之间的免疫共沉淀表明它们在大分子复合物中相关联。结合受影响Na+-K+-ATP酶构象的配体控制。在皮质中,γ(B)亚基的比例明显较低,γ(a)亚基在离体近曲小管细胞中占主导地位。通过免疫荧光,γ(B)-亚基仅在远曲小管和连接小管中检测到,它们富含Na+-K+-ATP酶,但占皮质质量的一小部分。在外髓质的外条和深层皮质的短距离内,粗的升支主要表达γ(B)亚单位。由于不同的机制维持和调节不同肾单位片段中的Na+稳态,因此γ亚基的剪接形式可能已经进化为通过泵特性、基因表达或两者来控制肾Na+泵。
Renal Na+-K+-ATPase is associated with the gamma-subunit (FXYD2), a single-span membrane protein that modifies ATPase properties. There are two splice variants with different amino termini, gamma(a) and gamma(b). Both were found in the inner stripe of the outer medulla in the thick ascending limb. Coimmunoprecipitation with each other and the alpha-subunit indicated that they were associated in macromolecular complexes. Association was controlled by ligands that affect Na+-K+-ATPase conformation. In the cortex, the proportion of the gamma(b)-subunit was markedly lower, and the gamma(a)-subunit predominated in isolated proximal tubule cells. By immunofluorescence, the gamma(b)-subunit was detected in the superficial cortex only in the distal convoluted tubule and connecting tubule, which are rich in Na+-K+-ATPase but comprise a minor fraction of cortex mass. In the outer stripe of the outer medulla and for a short distance in the deep cortex, the thick ascending limb predominantly expressed the gamma(b)-subunit. Because different mechanisms maintain and regulate Na+ homeostasis in different nephron segments, the splice forms of the gamma-subunit may have evolved to control the renal Na+ pump through pump properties, gene expression, or both.