Primary Cilium and Sonic Hedgehog Signaling During Neural Tube Patterning
Primary Cilium and Sonic Hedgehog Signaling During Neural Tube Patterning
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DOI：
10.1002/dneu.22193
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发表时间：
2015-04-01
影响因子：
3
通讯作者：
Mukhopadhyay, Saikat
中科院分区：
文献类型：
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作者：
Pal, Kasturi;Mukhopadhyay, Saikat
脊椎动物的腹侧神经管是由脊索和底板分泌的声刺猬（Shh）梯度形成的。正向遗传筛选首先指出初级纤毛在腹侧神经管模式中的作用。进一步的研究表明，Shh通路的大多数组分定位于初级纤毛或穿梭于初级纤毛。在没有Shh的情况下，双功能Gli转录因子以蛋白激酶A（PKA）和纤毛依赖的方式被蛋白水解加工成阻遏物形式。最近的工作表明，孤儿G蛋白偶联受体（GPCR）Gpr 161定位于纤毛，并作为一个负调节Shh信号通过确定Gli处理通过cAMP信号。初级纤毛也作为Shh通路中钙的信号传导隔室发挥作用。更好地理解纤毛作为信号室的作用，以及在信号传导过程中调节PKA活化和Gli扩增的第二信使系统的相互作用对于破译Shh在发育、神经元分化和肿瘤发生过程中的作用至关重要。(c)2014 Wiley Periodicals，Inc.开发神经生物学75：337-348，2015年
The ventral neural tube in vertebrates is patterned by a gradient of sonic hedgehog (Shh) secreted from the notochord and floor plate. Forward genetic screens first pointed to the role of the primary cilium in ventral neural tube patterning. Further research has shown that most components of the Shh pathway localize to or shuttle through the primary cilium. In the absence of Shh, the bifunctional Gli transcription factors are proteolytically processed into repressor forms in a protein kinase A (PKA)- and cilium-dependent manner. Recent work suggests that the orphan G-protein-coupled receptor (GPCR) Gpr161 localizes to cilia, and functions as a negative regulator of Shh signaling by determining Gli processing via cAMP signaling. The primary cilium also functions as a signaling compartment for calcium in the Shh pathway. A better understanding of the role of the cilium as a signaling compartment, and the interplay of second messenger systems that regulate PKA activation and Gli amplification during signaling is critical for deciphering the role of Shh during development, neuronal differentiation, and tumorigenesis. (c) 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 337-348, 2015