Normal lysosomal morphology and function in LAMP-1-deficient mice
Normal lysosomal morphology and function in LAMP-1-deficient mice
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DOI：
10.1074/jbc.274.18.12692
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发表时间：
1999-04-30
影响因子：
4.8
通讯作者：
Saftig, P
中科院分区：
文献类型：
--
作者：
Andrejewski, N;Punnonen, EL;Saftig, P
溶酶体膜含有两种高度糖基化的蛋白质，命名为LAMP-1和LAMP-2，作为主要组分。LAMP-1和LAMP-S在结构上是相关的，为了研究LAMP-1的生理作用，我们已经产生了这种蛋白质缺陷的小鼠。LAMP-1缺陷型小鼠是有活力的和能生育的。在LAMP-1缺陷的大脑中，观察到轻微的区域星形胶质细胞增生和对组织蛋白酶-D的免疫反应性改变。所有其他组织的组织学和超微结构分析未显示异常。与对照组相比，溶酶体性质，如酶活性、溶酶体pH值、渗透稳定性、密度、形状和亚细胞分布均未发生变化。LAMP-1缺陷和杂合子组织的蛋白质印迹分析显示LAR IP-S蛋白的上调，指出LAMP-S响应于LAMP-1缺陷的补偿作用。LAMP-2的增加既不与lamp-2 mRNA水平的增加相关，也不与LAMP-2半衰期的增加相关。
Lysosomal membranes contain two highly glycosylated proteins, designated LAMP-1 and LAMP-2, as major components. LAMP-1 and LAMP-S are structurally related, To investigate the physiological role of LAMP-1, we have generated mice deficient for this protein. LAMP-l-deficient mice are viable and fertile. In LAMP-1-deficient brain, a mild regional astrogliosis and altered immunoreactivity against cathepsin-D was observed. Histological and ultrastructural analyses of all other tissues did not reveal abnormalities. Lysosomal properties, such as enzyme activities, lysosomal pH, osmotic stability, density, shape, and subcellular distribution were not changed in comparison with controls. Western blot analyses of LAMP-1-deficient and heterozygote tissues revealed an up-regulation of the LAR IP-S protein pointing to a compensatory effect of LAMP-S in response to the LAMP-1 deficiency. The increase of LAMP-2 was neither correlated with an increase in the level of lamp-2 mRNAs nor with increased half-life time of LAMP-2, This findings suggest a translational regulation of LAMP-2 expression.