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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Acid Phosphatase 5 Is Responsible For Removing The Mannose 6-phosphate Recognition Marker From Lysosomal Proteins
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Acid Phosphatase 5 Is Responsible For Removing The Mannose 6-phosphate Recognition Marker From Lysosomal Proteins

机译：酸性磷酸酶5负责从溶酶体蛋白中去除甘露糖6-磷酸识别标记

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摘要

Most newly synthesized proteins destined for the lysosome reach this location via a specific intracellular pathway. In the Golgi, a phosphotransferase specifically labels lysosomal proteins with mannose 6-phosphate (Man-6-P). This modification is recognized by receptors that target the lysosomal proteins to the lysosome where, in most cell types, the Man-6-P recognition marker is rapidly removed. Despite extensive characterization of this pathway, the enzyme responsible for the removal of the targeting modification has remained elusive. In this study, we have identified this activity. Preliminary investigations using a cell-based bioassay were used to follow a dephosphorylation activity that was associated with the lysosomal fraction. This activity was high in the liver, where endogenous lysosomal proteins are efficiently dephosphorylated, but present at a much lower level in the brain, where the modification persists. This observation, combined with an analysis of the expression of lysosomal proteins in different tissues, led us to identify acid phosphatase 5 (ACP5) as a candidate for the enzyme that removes Man-6-P. Expression of ACP5 in N1E-115 neuroblas-toma cells, which do not efficiently dephosphorylate lysosomal proteins, significantly decreased the steady state levels of Man6-P glycoproteins. Analysis of ACP5-deficient mice revealed that levels of Man-6-P glycoproteins were highly elevated in tissues that normally express ACP5, and this resulted from a failure to dephosphorylate lysosomal proteins. These results indicate a central role for ACP5 in removal of the Man-6-P recognition marker and open up new avenues to investigate the importance of this process in cell biology and medicine.
机译：运用于溶酶体的大多数新合成蛋白质通过特定的细胞内途径到达该位置。在高尔基体中，磷酸转移酶用6-磷酸甘露糖（Man-6-P）特异性标记溶酶体蛋白。这种修饰被靶向溶酶体蛋白至溶酶体的受体识别，其中在大多数细胞类型中，Man-6-P识别标记被迅速去除。尽管对该途径进行了广泛表征，但负责去除靶向修饰的酶仍然难以捉摸。在这项研究中，我们已经确定了这项活动。使用基于细胞的生物测定的初步研究用于追踪与溶酶体级分相关的去磷酸化活性。在肝脏中这种活性很高，在肝脏中内源性溶酶体蛋白被有效地去磷酸化，但是在修饰持续存在的大脑中以较低的水平存在。该观察结果与对不同组织中溶酶体蛋白表达的分析相结合，使我们确定了酸性磷酸酶5（ACP5）作为可去除Man-6-P的酶的候选物。 ACP5在N1E-115神经鞘瘤细胞中的表达不能有效地使溶酶体蛋白去磷酸化，从而显着降低了Man6-P糖蛋白的稳态水平。对ACP5缺陷小鼠的分析显示，正常表达ACP5的组织中Man-6-P糖蛋白的水平高度升高，这是由于未能使溶酶体蛋白脱磷酸而引起的。这些结果表明，ACP5在去除Man-6-P识别标记中起着核心作用，并开辟了新途径来研究该过程在细胞生物学和医学中的重要性。

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