Washington University in St. Louis, Internal Medicine, Saint Louis, MO 63110, USA.
Mol Biol Cell. 2010 Nov 15;21(22):3773-5. doi: 10.1091/mbc.E10-05-0417.
We now recognize that a large number of membrane and soluble proteins contain covalently linked oligosaccharides that exhibit a vast array of structures and participate in a wide variety of biological processes. Nowhere is this better illustrated than the mannose 6-phosphate (Man-6-P) recognition system that mediates the trafficking of newly synthesized acid hydrolases to lysosomes in higher eukaryotes. The Asn-linked high-mannose oligosaccharides of these hydrolases facilitate folding of the nascent proteins in the endoplasmic reticulum via interaction with lectin-type chaperones and after phosphorylation in the Golgi, function as ligands for binding to Man-6-P receptors, a critical step in their transport to lysosomes. Failure to synthesize the Man-6-P recognition marker results in a serious lysosomal storage disease, one of a growing number of genetic conditions, termed congenital disorders of glycosylation, that result from faulty glycan biosynthesis.
我们现在认识到，大量的膜蛋白和可溶性蛋白含有共价连接的寡糖，这些寡糖表现出多种多样的结构，并参与多种生物过程。在这种情况下，没有比甘露糖 6-磷酸（Man-6-P）识别系统更好的例子了，该系统介导新合成的酸性水解酶在高等真核生物中向溶酶体的运输。这些水解酶的天冬酰胺连接的高甘露糖寡糖通过与凝集素型伴侣相互作用促进新生蛋白在内质网中的折叠，并且在高尔基体中磷酸化后，作为与 Man-6-P 受体结合的配体发挥作用，这是它们运输到溶酶体的关键步骤。如果不能合成 Man-6-P 识别标记，就会导致严重的溶酶体贮积病，这是越来越多的遗传疾病之一，称为先天性糖基化紊乱，是由于聚糖生物合成的缺陷引起的。
