Targeting of lysosomal acid phosphatase with altered carbohydrate.
Targeting of lysosomal acid phosphatase with altered carbohydrate.
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用改变的碳水化合物靶向溶酶体酸性磷酸酶。
DOI：
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发表时间：
1989
期刊：
影响因子：
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通讯作者：
K. von Figura
中科院分区：
文献类型：
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作者：
S. Gottschalk;A. Waheed;K. von Figura
人溶酶体酸性磷酸酶作为跨膜蛋白被转运到溶酶体，在那里它通过有限的蛋白水解被转化为可溶性蛋白（Waheed et al.，1988，EMBO J.7，2351-2358）。在损害甘露糖-6-磷酸受体依赖性转运、N-糖基化或N-连接寡糖加工的条件下，检查了人溶酶体酸性磷酸酶在异源BHK-21细胞中的转运。溶酶体酸性磷酸酶对溶酶体的靶向既不受阻断甘露糖-6-磷酸/IGF II受体的抗体的影响，也不受NH 4Cl的影响，NH 4Cl抑制可溶性溶酶体酶的甘露糖-6-磷酸受体依赖性靶向。1-脱氧野尻霉素、1-脱氧甘露野尻霉素和苦马豆素抑制N-连接寡糖在溶酶体酸性磷酸酶中的加工，而不显著影响其转运。衣霉素抑制溶酶体酸性磷酸酶的N-糖基化。非糖基化的溶酶体酸性磷酸酶多肽在轻膜内积累，并且不被转运到致密的溶酶体。这些结果表明，溶酶体酸性磷酸酶的转运是独立的甘露糖-6-磷酸受体，不涉及酸性pH值依赖性步骤，不需要处理的N-连接的寡糖。N-糖基化似乎是必要的，以实现运输能力形式的溶酶体酸性磷酸酶。
Human lysosomal acid phosphatase is transported as a transmembrane protein to lysosomes, where it is converted into a soluble protein by a limited proteolysis (Waheed et al., 1988, EMBO J. 7, 2351-2358). Transport of human lysosomal acid phosphatase in heterologous BHK-21 cells was examined under conditions that impair mannose-6-phosphate receptor-dependent transport, N-glycosylation or processing of N-linked oligosaccharides. Targeting of lysosomal acid phosphatase to lysosomes was neither affected by antibodies blocking the mannose-6-phosphate/IGF II receptor, nor by NH4Cl, which inhibited the mannose-6-phosphate receptor-dependent targeting of soluble lysosomal enzymes. 1-Deoxynojirimycin, 1-deoxymannojirimycin and swainsonine inhibited processing of N-linked oligosaccharides in lysosomal acid phosphatase without significantly affecting its transport. Tunicamycin inhibited N-glycosylation of lysosomal acid phosphatase. The non-glycosylated lysosomal acid phosphatase polypeptides accumulated within light membranes and were not transported to dense lysosomes. These results indicate that transport of lysosomal acid phosphatase is independent of mannose-6-phosphate receptors, does not involve an acid pH-dependent step and does not require processing of N-linked oligosaccharides. N-glycosylation appears to be necessary to achieve a transport competent form of lysosomal acid phosphatase.