Insulin-like growth factor II/cation-independent mannose 6-phosphate receptor and lysosomal enzyme recognition.
Insulin-like growth factor II/cation-independent mannose 6-phosphate receptor and lysosomal enzyme recognition.
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胰岛素样生长因子 II/非阳离子依赖性甘露糖 6-磷酸受体和溶酶体酶识别。
DOI：
10.1042/bst0240136
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发表时间：
1996
影响因子：
3.9
通讯作者：
Dahms,NM
中科院分区：
文献类型：
--
作者：
Dahms,NM
选择性地将新合成的溶酶体酶递送到溶酶体是溶酶体功能成熟过程中的一个重要过程，涉及到特定的识别和分离事件。在其生物合成过程中，可溶性酸性水解酶通过磷酸转移酶的作用在其N-连接的寡糖上获得甘露糖6-磷酸(Man-6-P)残基。磷酸转移酶识别溶酶体酶常见的蛋白质决定簇的能力提供了随后将溶酶体酶从分泌蛋白中分离出来所需的特异性[1-51]。在高尔基体中，磷甘露糖基残基作为高亲和力配体与两个不同的甘露糖6-磷酸受体(MPR)结合，即胰岛素样生长因子W阳离子非依赖性MPR(IGF-II/CI-MPR)和阳离子依赖MPR(CD-MPR)。当产生的受体-溶酶体酶复合体从高尔基体运输到酸化的内体隔室时，酸性水解酶就会从分泌途径中移除。低pH值导致该复合体的解离。释放的溶酶体酶随后被包装到溶酶体中，而受体要么返回高尔基体重复这一过程，要么移动到质膜，在那里，至少对IGF-II/CI-MPR来说，它们的功能是内化外源配体[6-81]。由于缺乏磷酸转移酶[9-11]，I细胞疾病(黏脂沉积症II)或假性Hurler多发性营养不良(黏脂沉积症111)患者的血清酸性水解酶水平升高[9-11]。本文综述了近年来有关IGF-II/CI-MPR结构决定因素与溶酶体结合酶结合的研究结果，从而证明了这种依赖于磷酸甘露糖的靶向途径的重要性。
The selective delivery of newly synthesized lysosomal enzymes to the lysosome is an essential process in the functional maturation of lysosomes that involves specific recognition and segregation events. During their biosynthesis, soluble acid hydrolases acquire mannose 6-phosphate (Man-6-P) residues on their N-linked oligosaccharides by the action of a phosphotransferase. The ability of the phosphotransferase to recognize a protein determinant which is common to lysosomal enzymes provides the specificity required for the subsequent segregation of lysosomal enzymes from secretory proteins [1-51. In the Golgi, phosphomannosyl residues serve as high-affinity ligands for binding to two distinct mannose 6-phosphate receptors (MPRs), the insulin-like growth factor Wcationindependent MPR (IGF-II/CI-MPR) and the cation-dependent MPR (CD-MPR). The removal of acid hydrolases from the secretory pathway occurs when the resulting receptor-lysosomal enzyme complex is transported from the Golgi to an acidified endosomal compartment. The low pH of this endosomal compartment induces the dissociation of the complex. The released lysosomal enzymes are then packaged into lysosomes while the receptors either return to the Golgi to repeat the process or move to the plasma membrane where, at least for the IGF-II/CI-MPR, they function to internalize exogenous ligands [6-81. The importance of this phosphomannosyldependent targeting pathway is borne out by the observation that patients with I-cell disease (mucolipidosis II) or pseudo-Hurler polydystrophy (mucolipidosis 111) have elevated levels of acid hydrolases in their serum due to a deficiency of the phosphotransferase [9-1 11. This article reviews the recent findings concerning the structural determinants of the IGF-II/CI-MPR that are involved in binding lysosomal enzymes.
巨噬细胞和相关细胞的碳水化合物识别蛋白
DOI：
--
发表时间：
1993
期刊：
影响因子：
--
作者：
Maureen E. Taylor
通讯作者：
Maureen E. Taylor