IDENTIFICATION AND CHARACTERIZATION OF CELLS DEFICIENT IN THE MANNOSE 6-PHOSPHATE RECEPTOR - EVIDENCE FOR AN ALTERNATE PATHWAY FOR LYSOSOMAL-ENZYME TARGETING
IDENTIFICATION AND CHARACTERIZATION OF CELLS DEFICIENT IN THE MANNOSE 6-PHOSPHATE RECEPTOR - EVIDENCE FOR AN ALTERNATE PATHWAY FOR LYSOSOMAL-ENZYME TARGETING
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DOI：
10.1073/pnas.80.3.775
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发表时间：
1983-01-01
期刊：
影响因子：
--
通讯作者：
KORNFELD, S
中科院分区：
文献类型：
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作者：
GABEL, CA;GOLDBERG, DE;KORNFELD, S
新合成的溶酶体酶获得磷酸甘露糖基单位，其允许酶与甘露糖6-磷酸受体结合并随后易位至溶酶体。在某些细胞类型中，这一系列事件对于将这些酶递送到溶酶体是必需的。使用黏菌溶酶体水解酶作为探针，鉴定了3个缺乏受体的鼠细胞系[白血病巨噬细胞P388 D细胞、肿瘤巨噬细胞J777·2细胞、肿瘤成纤维细胞L细胞]和1个含有非常低（3%）受体活性的细胞系[骨髓瘤MOPC 315细胞]。这些细胞系中的每一个都在其溶酶体酶上合成甘露糖6-磷酸识别标记物，但是，与具有高水平受体的细胞系不同，细胞积累含有磷酸单酯的寡糖。受体缺陷系具有高水平的细胞内酸水解酶活性，其包含在溶酶体特征性的致密颗粒中。在某些细胞中必须存在不依赖于甘露糖6-磷酸受体的细胞内机制，以将酸性水解酶递送到溶酶体细胞器。
Newly synthesized lysosomal enzymes acquire phosphomannosyl units, which allow binding of the enzymes to the mannose 6-phosphate receptor and subsequent translocation to lysosomes. In some cell types, this sequence of events is necessary for the delivery of these enzymes to lysosomes. Using a slime mold lysosomal hydrolase as a probe, 3 murine cell lines [leukemia macrophage P388D, cells, tumor macrophage J777.cntdot.2 cells, neoplastic fibroblast L cells] were identified that lack the receptor and 1 line [myeloma MOPC 315 cells] that contains very low (3%) receptor activity. Each of these lines synthesizes the mannose 6-phosphate recognition marker on its lysosomal enzymes, but, unlike cell lines with high levels of receptor, the cells accumulate oligosaccharides containing phosphomonoesters. The receptor-deficient lines possess high levels of intracellular acid hydrolase activity, which is contained in dense granules characteristic of lysosomes. Intracellular mechanisms independent of the mannose 6-phosphate receptor must exist in some cells for the delivery of acid hydrolases to lysosomal organelles.