纤毛
生物
鞭毛内运输
胶质3
音猬因子
细胞生物学
刺猬信号通路
神经管
信号转导
刺猬
纤毛形成
抑制因子
突变体
遗传学
转录因子
胚胎
基因
作者
Sutapa Mukhopadhyay,Xiaohui Wen,Navneet Ratti,Alexander V. Loktev,Linda Rangell,Suzie J. Scales,Peter K. Jackson
出处
期刊:Cell
[Elsevier]
日期:2013-01-01
卷期号:152 (1-2): 210-223
被引量:402
标识
DOI:10.1016/j.cell.2012.12.026
摘要
The primary cilium is required for Sonic hedgehog (Shh) signaling in vertebrates. In contrast to mutants affecting ciliary assembly, mutations in the intraflagellar transport complex A (IFT-A) paradoxically cause increased Shh signaling. We previously showed that the IFT-A complex, in addition to its canonical role in retrograde IFT, binds to the tubby-like protein, Tulp3, and recruits it to cilia. Here, we describe a conserved vertebrate G-protein-coupled receptor, Gpr161, which localizes to primary cilia in a Tulp3/IFT-A-dependent manner. Complete loss of Gpr161 in mouse causes midgestation lethality and increased Shh signaling in the neural tube, phenocopying Tulp3/IFT-A mutants. Constitutive Gpr161 activity increases cAMP levels and represses Shh signaling by determining the processing of Gli3 to its repressor form. Conversely, Shh signaling directs Gpr161 to be internalized from cilia, preventing its activity. Thus, Gpr161 defines a morphogenetic pathway coupling protein kinase A activation to Shh signaling during neural tube development.
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