Hedgehog induces opposite changes in turnover and subcellular localization of patched and smoothened
Hedgehog induces opposite changes in turnover and subcellular localization of patched and smoothened
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DOI：
10.1016/s0092-8674(00)00056-8
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发表时间：
2000-08-18
期刊：
影响因子：
64.5
通讯作者：
Cohen, SM
中科院分区：
文献类型：
--
作者：
Denef, N;Neubüser, D;Cohen, SM
Hedgehog家族分泌的信号蛋白在动物发育过程中组织空间格局。已鉴定出两种完整的膜蛋白，它们在Hedgehog信号转导中具有不同的作用。Hedgehog结合中的补丁功能，以及信号转导中的平滑功能。目前的模型认为补丁和光滑是一个预先形成的受体复合体，由Hedgehog结合激活。在这里，我们提出的证据是，在没有刺猬的情况下，补丁会破坏斯穆坦德的稳定。Hedgehog结合导致从细胞表面去除补丁。相反，Hedgehog导致细胞表面的磷酸化、稳定化和Smomoothed的积累。通过RNA介导的干扰去除细胞中的补丁也可以产生类似的效果。这些发现提出了补丁间接调节光滑活动的可能性。
Secreted signaling proteins of the Hedgehog family organize spatial pattern during animal development. Two integral membrane proteins have been identified with distinct roles in Hedgehog signaling. Patched functions in Hedgehog binding, and Smoothened functions in transducing the signal. Current models view Patched and Smoothened as a preformed receptor complex that is activated by Hedgehog binding. Here we present evidence that Patched destabilizes Smoothened in the absence of Hedgehog. Hedgehog binding causes removal of Patched from the cell surface. In contrast, Hedgehog causes phosphorylation, stabilization, and accumulation of Smoothened at the cell surface. Comparable effects can be produced by removing Patched from cells by RNA-mediated interference. These findings raise the possibility that Patched acts indirectly to regulate Smoothened activity.