The role of G protein-coupled receptors in cochlear planar cell polarity.
The role of G protein-coupled receptors in cochlear planar cell polarity.
复制标题
G 蛋白偶联受体在耳蜗平面细胞极性中的作用。
DOI：
10.1016/j.biocel.2016.02.011
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发表时间：
2016-08
期刊：
影响因子：
--
通讯作者：
Xu Zhigang
中科院分区：
文献类型：
--
作者：
Sun Jinpeng;Zhang Daolai;Wang Yanfei;Lin Hal;Yu Xiao;Xu Zhigang
平面细胞极性(PCP)被定义为细胞极性在组织平面上的协调排列，这对于细胞整合到组织中是重要的。PCP最好的例子之一是在耳蜗腺上皮。一些核心的PCP蛋白在PCP的调控中发挥重要作用，这些蛋白形成复合体，不对称地与细胞膜结合，介导细胞间的PCP信号转导。在PCP的核心蛋白中有两个G蛋白偶联受体(GPCRs)，Celsrand FrizzledGPCRs，这两个受体都在耳蜗PCP的调节中起重要作用。CelsrandFrizzled1、2、3和6在毛细胞或支持细胞的细胞膜上有不对称的定位。在动物模型中，Celsr1、Frizzled2和Frizzled3/6突变或基因敲除小鼠存在严重的耳蜗PCP缺陷。在G-α信号的下游，G-α-I与lgn和mInsc一起不对称地定位于毛细胞的顶面，以一种细胞自主的方式控制耳蜗毛乳头。GαI、LGN或mInsc的失活会导致小鼠耳蜗五氯苯酚的缺失。我们推测GPCRGαI偶联通过连接细胞间的PCP信号和细胞自主的PCP机制在耳蜗PCP的调节中起着关键作用。要全面了解耳蜗PCP的调控机制，还需要进一步的研究。
Planar cell polarity (PCP) is defined as the coordinated alignment of cell polarity across the tissue plane, which is important for the integration of cells into tissues. One of the best examples of PCP is in the cochlear epithelium. Several core PCP proteins have been identified to play important roles in PCP regulation, in which these proteins form complexes and associate with the cell membrane asymmetrically, mediating intercellular PCP signal transduction. Among the core PCP proteins are two G protein-coupled receptors (GPCRs),Celsrand Frizzled, both of which have been shown to play important roles in cochlear PCP regulation.CelsrandFrizzledgenes are expressed in the cochlear sensory epithelium, and Frizzled1, 2, 3 and 6 show asymmetric localizations on the cell membrane of hair cells or supporting cells. In the animal model,Celsr1,Frizzled2andFrizzled3/6mutant or knockout mice have profound cochlear PCP deficits. Downstream of GPCR signaling, Gαi was shown to asymmetrically localize on the apical surface of hair cells, together with LGN and mInsc, Gαi controls cochlear PCP in a cell-autonomous way. Inactivity of Gαi, LGN or mInsc results in PCP deficits in the mouse cochlea. We hypothesize that GPCR-Gαi coupling plays a pivotal role in cochlear PCP regulation via connecting the intercellular PCP signals with cell-autonomous PCP machinery. Further investigations are needed to fully understand the mechanism of cochlear PCP regulation.
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影响因子：
4.7
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