Expression of the transmembrane lysosomal protein SCARB2/Limp-2 in renin secretory granules controls renin release.

Nephron Experimental Nephrology Pub Date : 2012-01-01 Epub Date: 2013-04-26 DOI:10.1159/000350737
D Lee, M J Desmond, S A Fraser, M Katerelos, K Gleich, S F Berkovic, D A Power
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引用次数: 6

Abstract

Background/aims: Renin processing and storage is believed to occur in lysosome-like structures in the afferent arteriole. SCARB2/Limp-2 is a transmembrane lysosomal protein responsible for the intracellular trafficking of β-glucocerebrosidase. This study aimed to confirm the expression of SCARB2/Limp-2 in renin secretory granules, and explore its role in renin processing and secretion.

Methods: Co-localisation studies of (pro)renin with lysosomal membrane proteins, SCARB2/Limp-2, LAMP-1 and LAMP-2, were performed in mouse and human kidney sections. Intrarenal expression and secretion of (pro)renin in wild-type (WT) and Limp-2(-/-) mice were compared with and without stimulation.

Results: SCARB2/Limp-2, LAMP-1 and LAMP-2 co-localised with (pro)- renin in mouse and human kidney. Plasma renin concentration was increased in Limp-2(-/-) mice when compared to WT littermates. No change in (pro)renin expression, however, was observed in Limp-2(-/-) mouse kidney cortex by immunofluorescence microscopy, Western blotting, quantitative RT-PCR or the ultrastructural appearance of renin secretory granules. Acute stimulation of renin release by isoprenaline or hydralazine was similar in WT and Limp-2(-/-) mice. Following chronic salt restriction, however, immunofluorescence microscopy showed less (pro)renin expressed in Limp-2(-/-) compared with WT mouse kidneys, and there was significantly less prorenin but not renin by Western blotting in Limp-2(-/-) mouse kidney cortex, despite no difference in circulating renin levels.

Conclusion: Renin secretory granules possess integral lysosomal proteins, confirming that they are indeed modified lysosomes. Limp-2 deficiency leads to a minor increase in circulating renin. Limp-2, however, is not required for acute or chronic stimulation of renin release.

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肾素分泌颗粒中跨膜溶酶体蛋白 SCARB2/Limp-2 的表达控制着肾素的释放。
背景/目的:肾素的加工和储存被认为发生在传入动脉的溶酶体样结构中。SCARB2/Limp-2是一种跨膜溶酶体蛋白,负责β-葡糖脑苷脂的胞内转运。本研究旨在证实 SCARB2/Limp-2 在肾素分泌颗粒中的表达,并探讨其在肾素加工和分泌中的作用:方法:在小鼠和人类肾脏切片中进行了(原)肾素与溶酶体膜蛋白、SCARB2/Limp-2、LAMP-1 和 LAMP-2 的共定位研究。比较了野生型(WT)小鼠和 Limp-2(-/-)小鼠肾内(原)肾素的表达和分泌情况:结果:在小鼠和人类肾脏中,SCARB2/Limp-2、LAMP-1 和 LAMP-2 与(原)肾素共定位。与 WT 胎鼠相比,Limp-2(-/-)小鼠血浆肾素浓度升高。然而,通过免疫荧光显微镜、Western 印迹、定量 RT-PCR 或肾素分泌颗粒的超微结构外观,在 Limp-2(-/-)小鼠肾皮质中未观察到(原)肾素表达的变化。异丙肾上腺素或肼屈嗪对肾素释放的急性刺激在 WT 小鼠和 Limp-2(-/-)小鼠中相似。然而,在慢性盐限制后,免疫荧光显微镜显示,与WT小鼠肾脏相比,Limp-2(-/-)小鼠肾脏中表达的(原)肾素更少,尽管循环中肾素水平没有差异,但通过Western印迹检测,Limp-2(-/-)小鼠肾皮质中的原肾素显著减少,而肾素却没有减少:结论:肾素分泌颗粒具有完整的溶酶体蛋白,证实它们确实是经过修饰的溶酶体。Limp-2缺乏会导致循环肾素轻微增加。然而,Limp-2 并不是急性或慢性刺激肾素释放所必需的。
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Nephron Experimental Nephrology
Nephron Experimental Nephrology 医学-泌尿学与肾脏学
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