Specific alterations in levels of mannose 6-phosphorylated glycoproteins in different neuronal ceroid lipofuscinoses.
Specific alterations in levels of mannose 6-phosphorylated glycoproteins in different neuronal ceroid lipofuscinoses.
复制标题
不同神经元蜡样脂褐质中甘露糖 6-磷酸化糖蛋白水平的特定变化。
DOI：
10.1042/bj3340547
复制
发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Pullarkat,RK
中科院分区：
文献类型：
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作者：
Sleat,DE;Sohar,I;Pullarkat,PS;Lobel,P;Pullarkat,RK
甘露糖6-磷酸（Man-6-P）是在新合成的溶酶体蛋白上产生的碳水化合物修饰。这种修饰被两种Man-6-P受体特异性识别，所述Man-6-P受体指导溶酶体酶从高尔基体到前溶酶体区室的囊泡运输。Man-6-P在大多数细胞类型的溶酶体中被迅速去除;然而，在神经元中Man-6-P修饰持续存在。在这项研究中，我们已经研究了光谱的Man-6-P-含有糖蛋白的脑标本中的患者与不同的神经元蜡样脂褐质沉积症（NCL），这是进行性神经退行性疾病与溶酶体catalysts的缺陷建立联系。我们发现特征性的改变，在曼-6-P糖蛋白的标本从晚婴儿（LINCL），青少年（JNCL）和成人（ANCL）患者。LINCL患者的Man-6-P糖蛋白与对照组相似，除了与CLN 2（一种最近鉴定的溶酶体酶，其缺陷导致这种疾病）对应的条带不存在。在ANCL患者中，与正常对照组相比，两种Man-6-P糖蛋白升高，表明这种疾病也是由于溶酶体水解的扰动。在JNCL中，Man-6-P糖蛋白的总水平是对照组的7倍。在一般情况下，这反映了增加的溶酶体酶活性在JNCL，但三个曼-6-P糖蛋白升高到更大的程度。这些是CLN 2和在ANCL中也高度升高的未鉴定的蛋白质。
Mannose 6-phosphate (Man-6-P) is a carbohydrate modification that is generated on newly synthesized lysosomal proteins. This modification is specifically recognized by two Man-6-P receptors that direct the vesicular transport of the lysosomal enzymes from the Golgi to a prelysosomal compartment. The Man-6-P is rapidly removed in the lysosome of most cell types; however, in neurons the Man-6-P modification persists. In this study we have examined the spectrum of Man-6-P-containing glycoproteins in brain specimens from patients with different neuronal ceroid lipofuscinoses (NCLs), which are progressive neurodegenerative disorders with established links to defects in lysosomal catabolism. We find characteristic alterations in the Man-6-P glycoproteins in specimens from late-infantile (LINCL), juvenile (JNCL) and adult (ANCL) patients. Man-6-P glycoproteins in LINCL patients were similar to controls, with the exception that the band corresponding to CLN2, a recently identified lysosomal enzyme whose deficiency results in this disease, was absent. In an ANCL patient, two Man-6-P glycoproteins were elevated in comparison with normal controls, suggesting that this disease also results from a perturbation in lysosomal hydrolysis. In JNCL, total levels of Man-6-P glycoproteins were 7-fold those of controls. In general this was reflected by increased lysosomal enzyme activities in JNCL but three Man-6-P glycoproteins were elevated to an even greater degree. These are CLN2 and the unidentified proteins that are also highly elevated in the ANCL.