Accumulation of autophagic vacuoles and cardiomyopathy in LAMP-2-deficient mice
Accumulation of autophagic vacuoles and cardiomyopathy in LAMP-2-deficient mice
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DOI：
10.1038/35022595
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发表时间：
2000-08-24
期刊：
影响因子：
64.8
通讯作者：
Saftig, P
中科院分区：
文献类型：
--
作者：
Tanaka, Y;Guhde, G;Saftig, P
溶酶体相关膜蛋白-2（LAMP-2）是一种高度糖基化的蛋白质，是溶酶体膜的重要组成部分（1-7）。在这里，我们表明，LAMP-2缺乏症的小鼠死亡率增加20至40天的年龄。存活的小鼠具有生育能力，寿命几乎正常。在超微结构上，自噬空泡在许多组织中广泛积聚，包括肝、胰腺、脾、肾、骨骼肌和心肌。在肝细胞中，长寿命蛋白质的自噬降解严重受损。心肌细胞超微结构异常，心脏收缩力严重降低。这些发现表明LAMP-2对自噬至关重要。这一理论进一步得到以下发现的证实：导致Danon病的人LAMP-2缺陷（8）与横纹肌细胞中自噬物质的积累有关。
Lysosome-associated membrane protein-2 (LAMP-2) is a highly glycosylated protein and an important constituent of the lysosomal membrane(1-7). Here we show that LAMP-2 deficiency in mice increases mortality between 20 and 40 days of age. The surviving mice are fertile and have an almost normal life span. Ultrastructurally, there is extensive accumulation of autophagic vacuoles in many tissues including liver, pancreas, spleen, kidney and skeletal and heart muscle. In hepatocytes, the autophagic degradation of long-lived proteins is severely impaired. Cardiac myocytes are ultrastructurally abnormal and heart contractility is severely reduced. These findings indicate that LAMP-2 is critical for autophagy. This theory is further substantiated by the finding that human LAMP-2 deficiency(8) causing Danon's disease is associated with the accumulation of autophagic material in striated myocytes.