Apical secretion of Wnt1 in polarized epithelial cells is regulated by exocyst-mediated trafficking.
Apical secretion of Wnt1 in polarized epithelial cells is regulated by exocyst-mediated trafficking.
复制标题
极化上皮细胞中 Wnt1 的顶端分泌受到外囊介导的运输的调节。
DOI：
10.1093/jb/mvx035
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
A.
中科院分区：
文献类型：
--
作者：
Yamamoto;H.;Sato;A.;and Kikuchi;A.
Wnt是从包括间充质细胞、造血细胞和上皮细胞的各种细胞类型分泌的糖基化蛋白。Wnt在极化上皮细胞中的定向分泌是独特的; Wnt 11在顶端分泌，而Wnt 5a和Wnt 3a在基底外侧分泌。在这里，我们发现，Wnt 1是等效的分泌在MDCK细胞的顶部和基底外侧。Wnt 1在Asn 29和Asn 359处被复合型或混合型聚糖修饰，在Asn 316处被高甘露糖型或混合型聚糖修饰。虽然Wnt 11在N-末端位点的糖基化被证明是其顶端分泌所必需的，但Wnt 1的Asn 29的糖基化不是必需的。相反，顶端分泌的Wnt 1被抑制敲低Sec 6和Sec 8，表明Wnt 1分泌顶端通过外囊介导的运输。Wnt 1的基底外侧分泌由网格蛋白和AP-1介导，其机制类似于Wnt 5a和Wnt 3a所使用的机制。虽然Wingless被报道被转胞吞到果蝇翼盘的基底外侧区域，但转胞吞并不参与Wnt 1的基底外侧分泌。因此，Wnt 1的极化分泌受与其他Wnt不同的机制调节。
Wnts are glycosylated proteins secreted from various cell types including mesenchymal, hematopoietic and epithelial cells. Directional secretion of Wnts in polarized epithelial cells is unique; Wnt11 is secreted apically, whereas Wnt5a and Wnt3a are secreted basolaterally. Here, we found that Wnt1 is equivalently secreted both apically and basolaterally in MDCK cells. Wnt1 was modified with a complex- or hybrid-type glycan at Asn29 and Asn359 and the high-mannose- or hybrid-type glycan at Asn316. Although glycosylation of Wnt11 at the N-terminal site was shown to be essential for its apical secretion, glycosylation of Asn29 of Wnt1 was not required. Instead, the apical secretion of Wnt1 was inhibited by knockdown of Sec6 and Sec8, suggesting that Wnt1 is secreted apically via exocyst-mediated transport. Basolateral secretion of Wnt1 was mediated by clathrin and AP-1, in mechanism similar to that used by Wnt5a and Wnt3a. Although Wingless was reported to be transcytosed to the basolateral region in theDrosophilawing disc, transcytosis was not involved in the basolateral secretion of Wnt1. Thus, the polarized secretion of Wnt1 is regulated by different mechanisms than other Wnts.