Analysis of the mechanisms of megalin-mediated intracellular signaling and urinary megalin excretion

近曲小管内吞受体megalin是一种膜蛋白，参与肾小球滤过蛋白的重吸收和代谢。此外，Meggalin的胞外结构域被认为是通过一些病理刺激通过调节的膜内蛋白分解(RIP)从细胞膜上分离出来的，而Meggalin的细胞质结构域(MCD)可能被释放出来用于细胞内信号传递，在肾脏疾病的发生和发展中发挥着重要作用。为了建立肾脏疾病的新的诊断和治疗策略，我们分析了MCD与其他细胞内分子相互作用的机制。结果提示，Megalin的RIP和MCD与细胞内适配蛋白的分子相互作用可能参与了急性肾损伤的发病机制。

Proximal tubular endocytic receptor megalin is a membrane protein involved in reabsorption and metabolism of glomerular-filtrated proteins. Also, megalin's extracellular domain is thought to be cleaved from cellular membranes by regulated intramembrane proteolysis (RIP) via some pathological stimuli, while megalin's cytoplasmic domain (MCD) may be released for intracellular signaling, playing an important role in the development and progression of kidney disease. To establish novel diagnostic and therapeutic strategies for kidney disease, we analyzed the mechanisms of molecular interaction of MCD with other intracellular molecules. As a result, it was suggested that RIP of megalin and molecular interaction of MCD with intracellular adapter proteins may be involved in the pathogenesis of acute kidney injury in an experimental ischemia-reperfusion model.