PTK7 localization and protein stability is affected by canonical Wnt ligands
PTK7 localization and protein stability is affected by canonical Wnt ligands
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DOI：
10.1242/jcs.198580
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发表时间：
2017-06-01
影响因子：
4
通讯作者：
Borchers, Annette
中科院分区：
文献类型：
--
作者：
Berger, Hanna;Breuer, Marlen;Borchers, Annette
蛋白酪氨酸激酶7 （PTK7）是一种进化保守的跨膜受体，在胚胎发育和疾病中起重要作用。它最初被认为是结肠癌中上调的一个基因，后来被证明可以调节平面细胞极性（PCP）和定向细胞运动。PTK7是Wnt共受体；然而，其在Wnt信号传导中的作用仍存在争议。在这里，我们发现证据表明PTK7位于规范和非规范Wnt信号通路的交叉点。在典型Wnt配体存在的情况下，PTK7受小窝蛋白介导的内吞作用的影响，而不受非典型Wnt配体的影响。PTK7的内吞作用依赖于PTK7共受体Fz7（也称为Fzd7）的存在，并导致PTK7的溶酶体降解。正如我们之前观察到的那样，PTK7激活非规范PCP Wnt信号，但抑制规范Wnt信号，我们的数据表明规范和PTK7 Wnt信号相互抑制。PTK7可能通过结合典型Wnt配体来抑制典型Wnt信号传导，从而阻止它们与Wnt受体相互作用，否则Wnt受体将支持典型Wnt信号传导。相反，如果典型的Wnt蛋白与PTK7受体相互作用，它们会诱导其内化和降解。
Protein tyrosine kinase 7 (PTK7) is an evolutionarily conserved transmembrane receptor with important roles in embryonic development and disease. Originally identified as a gene upregulated in colon cancer, it was later shown to regulate planar cell polarity (PCP) and directional cell movement. PTK7 is a Wnt co-receptor; however, its role in Wnt signaling remains controversial. Here, we find evidence that places PTK7 at the intersection of canonical and non-canonical Wnt signaling pathways. In presence of canonical Wnt ligands PTK7 is subject to caveolin-mediated endocytosis, while it is unaffected by non-canonical Wnt ligands. PTK7 endocytosis is dependent on the presence of the PTK7 co-receptor Fz7 (also known as Fzd7) and results in lysosomal degradation of PTK7. As we previously observed that PTK7 activates non-canonical PCP Wnt signaling but inhibits canonical Wnt signaling, our data suggest a mutual inhibition of canonical and PTK7 Wnt signaling. PTK7 likely suppresses canonical Wnt signaling by binding canonical Wnt ligands thereby preventing their interaction with Wnt receptors that would otherwise support canonical Wnt signaling. Conversely, if canonical Wnt proteins interact with the PTK7 receptor, they induce its internalization and degradation.