Lrp4 modulates extracellular integration of cell signaling pathways in development.
Lrp4 modulates extracellular integration of cell signaling pathways in development.
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DOI：
10.1371/journal.pone.0004092
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发表时间：
2008
期刊：
影响因子：
3.7
通讯作者：
Sharpe PT
中科院分区：
文献类型：
--
作者：
Ohazama A;Johnson EB;Ota MS;Choi HY;Porntaveetus T;Oommen S;Itoh N;Eto K;Gritli-Linde A;Herz J;Sharpe PT
细胞信号传导在细胞外整合的程度目前还不清楚。我们表明，低密度受体相关蛋白家族的成员，Lrp 4调制和整合BMP和典型的Wnt信号在牙齿形态发生结合分泌的BMP拮抗剂蛋白明智的。Lrp 4和Wise的小鼠突变体表现出相同的牙齿表型，包括多生门齿和臼齿以及融合臼齿。我们提出Lrp 4/Wise相互作用作为上皮间充质细胞信号传导的细胞外整合剂。明智的是，从间充质细胞分泌的蛋白质与BMP结合，也与在上皮细胞上表达的Lrp 4结合。这种结合然后导致上皮细胞中Wnt活性的调节。因此，在这种情况下，Wise作为细胞外信号分子连接两个信号通路。我们进一步表明，这种整合的下游介质是Shh信号通路。
The extent to which cell signaling is integrated outside the cell is not currently appreciated. We show that a member of the low-density receptor-related protein family, Lrp4 modulates and integrates Bmp and canonical Wnt signalling during tooth morphogenesis by binding the secreted Bmp antagonist protein Wise. Mouse mutants of Lrp4 and Wise exhibit identical tooth phenotypes that include supernumerary incisors and molars, and fused molars. We propose that the Lrp4/Wise interaction acts as an extracellular integrator of epithelial-mesenchymal cell signaling. Wise, secreted from mesenchyme cells binds to BMP's and also to Lrp4 that is expressed on epithelial cells. This binding then results in the modulation of Wnt activity in the epithelial cells. Thus in this context Wise acts as an extracellular signaling molecule linking two signaling pathways. We further show that a downstream mediator of this integration is the Shh signaling pathway.
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