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Apical Sorting by Galectin-3-Dependent Glycoprotein Clustering

机译：通过Galectin-3依赖性糖蛋白聚类进行心尖排序

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摘要

Epithelial cells are characterized by their polarized organization based on an apical membrane that is separated from the basolateral membrane domain by tight junctions. Maintenance of this morphology is guaranteed by highly specific sorting machinery that separates lipids and proteins into different carrier populations for the apical or basolateral cell surface. Lipid-raft-independent apical carrier vesicles harbour the beta-galactoside-bind-ing lectin galectin-3, which interacts directly with apical cargo in a glycan-dependent manner. These glycopro-teins are mistargeted to the basolateral membrane in galectin-3-depleted cells, dedicating a central role to this lectin in raft-independent sorting as apical receptor. Here, we demonstrate that high-molecular-weight clusters are exclusively formed in the presence of galectin-3. Their stability is sensitive to increased carbohydrate concentrations, and cluster formation as well as apical sorting are perturbed in glycosylation-deficient Madin-Darby canine kidney (MDCK) II cells. Together, our data suggest that glycoprotein cross-linking by galectin-3 is required for apical sorting of non-raft-associated cargo.
机译：上皮细胞的特征是其极化组织基于顶膜，该顶膜通过紧密连接与基底外侧膜域隔开。高度特异性的分选机制可确保维持这种形态，该分选机制可将脂质和蛋白质分离为顶端或基底外侧细胞表面的不同载体。不依赖脂质筏的顶端载体囊泡带有β-半乳糖苷结合凝集素galectin-3，后者以糖基依赖性方式直接与顶端货物相互作用。这些糖蛋白在半乳糖凝集素3缺失的细胞中被错误地靶向了基底外侧膜，这在凝乳素的分离中作为根尖受体在这种凝集素中起着核心作用。在这里，我们证明高分子量簇仅在存在galectin-3的情况下形成。它们的稳定性对增加的碳水化合物浓度敏感，在糖基化缺陷的Madin-Darby犬肾（MDCK）II细胞中干扰了簇的形成以及根尖分选。在一起，我们的数据表明，galectin-3交联的糖蛋白是非筏相关货物的顶端分类所必需的。

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