Association of dishevelled with the clathrin AP-2 adaptor is required for frizzled endocytosis and planar cell polarity signaling
Association of dishevelled with the clathrin AP-2 adaptor is required for frizzled endocytosis and planar cell polarity signaling
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DOI：
10.1016/j.devcel.2006.10.015
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发表时间：
2007-01-01
影响因子：
11.8
通讯作者：
Kirchhausen, Tomas
中科院分区：
文献类型：
--
作者：
Yu, Anan;Rual, Jean-Francois;Kirchhausen, Tomas
当被Wnt激活时，Frizzled型受体被内化，这一过程需要招募Dhevelled型。我们描述了Dishevelled2(Dvl2)和clathrin适配器AP-2的一个亚基mu2-Adaptin之间的一种新的相互作用；这种相互作用是激活的Frizzled4与内吞机制及其内化所必需的。Dvl2与AP-2的相互作用需要Dvl2中的DEP结构域和YHEL基序同时与mu2的C末端结合。YheL基序中的Dvl2突变体不能与mu2和ap-2结合，也不能阻止Frizzled4内化。相应的非洲爪哇杂乱突变体表现出干扰平面细胞极性(PCP)途径介导的原肠形成的能力受损。相反，在PCP信号中受损的Dvl2突变体在其DEP结构域表现出缺陷的AP-2相互作用，并阻止Frizzled4的内化。我们认为Dvl2与AP-2的直接相互作用对Frizzled内化和FrizzledPCP信号转导具有重要意义。
Upon activation by Wnt, the Frizzled receptor is internalized in a process that requires the recruitment of Dishevelled. We describe a novel interaction between Dishevelled2 (Dvl2) and mu 2-adaptin, a subunit of the clathrin adaptor AP-2; this interaction is required to engage activated Frizzled4 with the endocytic machinery and for its internalization. The interaction of Dvl2 with AP-2 requires simultaneous association of the DEP domain and a peptide YHEL motif within Dvl2 with the C terminus of mu 2. Dvl2 mutants in the YHEL motif fail to associate with mu 2 and AP-2, and prevent Frizzled4 internalization. Corresponding Xenopus Dishevelled mutants show compromised ability to interfere with gastrulation mediated by the planar cell polarity (PCP) pathway. Conversely, a Dvl2 mutant in its DEP domain impaired in PCP signaling exhibits defective AP-2 interaction and prevents the internalization of Frizzled4. We suggest that the direct interaction of Dvl2 with AP-2 is important for Frizzled internalization and Frizzled/PCP signaling.