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在声波刺猬信号接收中，Smurf介导的果蝇patched1蛋白内吞作用的必要性。

Requirement of Smurf-mediated endocytosis of Patched1 in sonic hedgehog signal reception.

作者信息

Yue Shen, Tang Liu-Ya, Tang Ying, Tang Yi, Shen Qiu-Hong, Ding Jie, Chen Yan, Zhang Zengdi, Yu Ting-Ting, Zhang Ying E, Cheng Steven Y

机构信息

Department of Developmental Genetics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.

Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, United States.

出版信息

Elife. 2014 Jun 12;3:e02555. doi: 10.7554/eLife.02555.

DOI:10.7554/eLife.02555
PMID:24925320
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4080449/
Abstract

Cell surface reception of Sonic hedgehog (Shh) must ensure that the graded morphogenic signal is interpreted accordingly in neighboring cells to specify tissue patterns during development. Here, we report endocytic sorting signals for the receptor Patched1 (Ptch1), comprising two 'PPXY' motifs, that direct it to degradation in lysosomes. These signals are recognized by two HECT-domain ubiquitin E3 ligases, Smurf1 and Smurf2, which are induced by Shh and become enriched in Caveolin-1 lipid rafts in association with Ptch1. Smurf-mediated endocytic turnover of Ptch1 is essential for its clearance from the primary cilium and pathway activation. Removal of both Smurfs completely abolishes the ability of Shh to sustain the proliferation of postnatal granule cell precursors in the cerebellum. These findings reveal a novel step in the Shh pathway activation as part of the Ptch1 negative feedback loop that precisely controls the signaling output in response to Shh gradient signal.

摘要

音猬因子（Shh）的细胞表面受体必须确保相邻细胞能够相应地解读这种梯度形态发生信号，以在发育过程中确定组织模式。在此，我们报告了受体patched1（Ptch1）的内吞分选信号，其由两个“PPXY”基序组成，这些基序将Ptch1导向溶酶体进行降解。这些信号被两种HECT结构域泛素E3连接酶Smurf1和Smurf2识别，它们由Shh诱导，并与Ptch1一起在小窝蛋白1脂筏中富集。Smurf介导的Ptch1内吞周转对于其从初级纤毛的清除和信号通路激活至关重要。去除这两种Smurf完全消除了Shh维持小脑产后颗粒细胞前体增殖的能力。这些发现揭示了Shh信号通路激活中的一个新步骤，这是Ptch1负反馈回路的一部分，该回路精确控制响应Shh梯度信号的信号输出。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee3c/4080449/726b3f19d65f/elife02555f011.jpg
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