The two endocytic pathways mediated by the carbohydrate recognition domain and regulated by the collagen-like domain of galectin-3 in vascular endothelial cells.

The two endocytic pathways mediated by the carbohydrate recognition domain and regulated by the collagen-like domain of galectin-3 in vascular endothelial cells.
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血管内皮细胞中碳水化合物识别域介导并受Galectin-3胶原样域调节的两条内吞途径

DOI:
10.1371/journal.pone.0052430
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Tai G
Tai G
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Gao X;Liu D;Fan Y;Li X;Xue H;Ma Y;Zhou Y;Tai G

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Galectin-3在内皮细胞形态发生和血管生成中起重要作用。我们研究了Galectin-3在人血管内皮细胞中的内吞作用,发现Galectin-3可以以糖依赖的方式与细胞结合并内化到细胞内。我们的工作还揭示了Galectin-3被转运到早期/再循环的内体,然后被分成两条途径--循环回质膜或靶向晚期的内体/溶酶体。构建了不同N端和C端截短形式的Galectin-3,并与全长蛋白进行了比较。这些比较表明,Galectin-3的碳水化合物识别结构域是Galectin-3结合和内吞所必需的。该蛋白的N-末端由N-末端前导结构域和胶原样内部重复结构域组成,不能单独介导结合和内吞作用。胶原样结构域虽然在很大程度上与Galectin-3转运到早期/再循环内体无关,但它是将Galectin-3靶向晚期内体/溶酶体所必需的。相反,前导结构域与结合和细胞内转运无关。这项研究提供的数据与全长和截短的Galectin-3诱导的不同细胞行为很好地关联,并为理解其血管生成机制提供了另一种方式。
Galectin-3 plays an important role in endothelial morphogenesis and angiogenesis. We investigated the endocytosis of galectin-3 in human vascular endothelial cells and showed that galectin-3 could associate with and internalized into the cells in a carbohydrate-dependent manner. Our work also revealed that galectin-3 was transported to the early/recycling endosomes and then partitioned into two routes – recycling back to the plasma membrane or targeting to the late endosomes/lysosomes. Various N- and C-terminal truncated forms of galectin-3 were constructed and compared with the full-length protein. These comparisons showed that the carbohydrate-recognition domain of galectin-3 was required for galectin-3 binding and endocytosis. The N-terminal half of the protein, which comprises the N-terminal leader domain and the collagen-like internal repeating domain, could not mediate binding and endocytosis alone. The collagen-like domain, although it was largely irrelevant to galectin-3 trafficking to the early/recycling endosomes, was required for targeting galectin-3 to the late endosomes/lysosomes. In contrast, the leader domain was irrelevant to both binding and intracellular trafficking. The data presented in this study correlate well with different cellular behaviors induced by the full-length and the truncated galectin-3 and provide an alternative way of understanding its angiogenic mechanisms.
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发表时间: 2010-08-30
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