LYSOSOMAL-ENZYME BINDING TO MOUSE P388D1 MACROPHAGE MEMBRANES LACKING THE 215-KDA MANNOSE 6-PHOSPHATE RECEPTOR - EVIDENCE FOR THE EXISTENCE OF A 2ND MANNOSE 6-PHOSPHATE RECEPTOR

LYSOSOMAL-ENZYME BINDING TO MOUSE P388D1 MACROPHAGE MEMBRANES LACKING THE 215-KDA MANNOSE 6-PHOSPHATE RECEPTOR - EVIDENCE FOR THE EXISTENCE OF A 2ND MANNOSE 6-PHOSPHATE RECEPTOR
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DOI:
10.1073/pnas.82.13.4428
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发表时间:
1985-01-01
影响因子:
11.1
通讯作者:
KORNFELD, S
KORNFELD, S
中科院分区:
综合性期刊1区
文献类型:
--
作者:
HOFLACK, B;KORNFELD, S

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小鼠 P388D1 巨噬细胞将新合成的酸性水解酶靶向溶酶体,尽管它们缺乏 215 kDa [千道尔顿] 甘露糖 6-磷酸 (Man-6-P) 受体。这些细胞含有与膜相关的 Man-6-P 受体,该受体与之前描述的受体不同。新受体结合含有磷酸甘露糖残基的溶酶体酶。这种结合可被 Man-6-P 或用碱性磷酸酶预处理溶酶体酶抑制。溶酶体酶结合发生在中性 pH 值下,结合配体的解离发生在低 pH 值下,与内体或溶酶体内发现的情况相当。新受体与 215-kDa Man-6-P 受体有两个不同之处。它对二价阳离子有绝对的要求,并且不能结合盘基网柄菌溶酶体酶,该酶含有甲基磷酸甘露糖基残基而不是常见的磷酸甘露糖基单酯。根据阳离子需求的差异,2154-kDa 受体可能被称为 Man-6-P 受体 CI(阳离子非依赖性),而新受体可能被称为 Man-6-P 受体 CD(阳离子依赖性)。 Man-6-P 受体 CD 的作用是将新合成的酸性水解酶靶向 P388D1 巨噬细胞中的溶酶体。
Mouse P388D1 macrophages target newly synthesized acid hydrolases to lysosomes in spite of their lack of the 215-kDa [kilodalton] mannose 6-phosphate (Man-6-P) receptor. These cells contain a membrane-associated Man-6-P receptor that is distinct from the previously described receptor. The new receptor binds lysosomal enzymes containing phosphomannosyl residues. This binding is inhibited by Man-6-P or by pretreatment of the lysosomal enzymes with alkaline phosphatase. Lysosomal enzyme binding occurs at neutral pH and dissociation of the bound ligand occurs at low pH values comparable to those found within endosomes or lysosomes. The new receptor differs from the 215-kDa Man-6-P receptor in 2 ways. It has an absolute requirement for divalent cations and is unable to bind Dictyostelium discoideum lysosomal enymes, which contain methylphosphomannosyl residues rather than the usual phosphomannosyl monoesters. Based on the difference in cation requirement, the 2154-kDa receptor might be referred to as Man-6-P receptor CI (cation independent) and the new receptor as Man-6-P receptor CD (cation dependent). The Man-6-P receptor CD functions in the targeting of newly synthesized acid hydrolases to lysosomes in P388D1 macrophages.