CHIP28 water channels are localized in constitutively water-permeable segments of the nephron.
CHIP28 water channels are localized in constitutively water-permeable segments of the nephron.
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DOI：
10.1083/jcb.120.2.371
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发表时间：
1993-01
期刊：
影响因子：
--
通讯作者：
Agre P
中科院分区：
文献类型：
--
作者：
Nielsen S;Smith BL;Christensen EI;Knepper MA;Agre P
沿肾单位的水运输部位已有很好的描述，但肾脏水运输的分子基础仍知之甚少。CHIP28是一种28kD的完整蛋白，被认为是调节红细胞和肾脏跨膜水运动的蛋白质(Preston，G.M.，T.P.Carroll，W.B.Guggino和P.Agre)。1992年。科学[华盛顿州]DC]。256：385-387)。为了确定CHIP28是否可以解释肾上皮水转运，我们使用了特异性的多克隆抗体，利用光镜和电子显微镜在细胞和亚细胞水平对CHIP28进行了定量和定位。CHIP28占分离的近端小管刷状边缘蛋白的3.8%。除S1段的前几个细胞外，CHIP28免疫定位于近端曲小管和直小管，见于顶刷缘的微绒毛和基底侧膜。CHIP28在近端小管内吞小泡或其他细胞内结构中检测到极少的CHIP28。CHIP28在细小降支肢体的顶端和基底外侧膜上也观察到不间断的强免疫染色，包括Henle的短环和长环。这些肾单位具有结构性的高渗透水渗透性。CHIP28在细长的升支、粗大的升支和高度不透水的远端小管中均未检测到。此外，CHIP28在集合管上皮细胞中未检测到，集合管上皮细胞的水通透性由抗利尿激素调节。这些丰度和结构组织的测定提供了证据，证明CHIP28水通道是近端小管和Henle‘s环降支结构性跨上皮水运输的主要途径。
The sites of water transport along the nephron are well characterized, but the molecular basis of renal water transport remains poorly understood. CHIP28 is a 28-kD integral protein which was proposed to mediate transmembrane water movement in red cells and kidney (Preston, G. M., T. P. Carroll, W. B. Guggino, and P. Agre. 1992. Science [Wash. DC]. 256:385-387). To determine whether CHIP28 could account for renal epithelial water transport, we used specific polyclonal antibodies to quantitate and localize CHIP28 at cellular and subcellular levels in rat kidney using light and electron microscopy. CHIP28 comprised 3.8% of isolated proximal tubule brush border protein. Except for the first few cells of the S1 segment, CHIP28 was immunolocalized throughout the convoluted and straight proximal tubules where it was observed in the microvilli of the apical brush border and in basolateral membranes. Very little CHIP28 was detected in endocytic vesicles or other intracellular structures in proximal tubules. Uninterrupted, heavy immunostaining of CHIP28 was also observed over both apical and basolateral membranes of descending thin limbs, including both short and long loops of Henle. These nephron sites have constitutively high osmotic water permeabilities. CHIP28 was not detected in ascending thin limbs, thick ascending limbs, or distal tubules, which are highly impermeable to water. Moreover, CHIP28 was not detected in collecting duct epithelia, where water permeability is regulated by antidiuretic hormone. These determinations of abundance and structural organization provide evidence that the CHIP28 water channel is the predominant pathway for constitutive transepithelial water transport in the proximal tubule and descending limb of Henle's loop.