Loss of the Heparan Sulfate Proteoglycan Glypican5 Facilitates Long-Range Sonic Hedgehog Signaling.
Loss of the Heparan Sulfate Proteoglycan Glypican5 Facilitates Long-Range Sonic Hedgehog Signaling.
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DOI：
10.1002/stem.3018
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发表时间：
2019-07
期刊：
影响因子：
--
通讯作者：
Roelink H
中科院分区：
文献类型：
--
作者：
Guo W;Roelink H
作为形态学，声音刺猬（SHH）介导了距离合成部位距离的信号传导。分泌后，SHH必须穿过细胞外基质（ECM）的距离才能到达目标细胞并激活HH响应。尤其是Glypican家族的ECM蛋白，尤其是硫酸乙酰肝素蛋白聚糖（HSPG），对SHH信号的负面影响和正面影响都归因于其结合SHH的能力。使用小鼠胚胎干细胞衍生的镶嵌组织与缺乏糖基转移酶exostosin1和exostosin2或HSPG核心蛋白Glypican5的隔室，我们表明，当SHH周围围绕其源细胞积聚，当它们被具有突变的ECM的细胞包围时。 SHH的积累与非电池自主SHH响应的增加相关。我们的结果支持一个模型，其中SHH在细胞表面上呈现在缺乏HSPG的ECM处或附近，这可能是由于缺乏这些SHH隔离分子。
As a morphogen, Sonic Hedgehog (Shh) mediates signaling at a distance from its sites of synthesis. After secretion, Shh must traverse a distance through the extracellular matrix (ECM) to reach the target cells and activate the Hh response. ECM proteins, in particular, the heparan sulfate proteoglycans (HSPGs) of the glypican family, have both negative and positive effects on Shh signaling, all attributed to their ability to bind Shh. Using mouse embryonic stem cell-derived mosaic tissues with compartments that lack the glycosyltransferases Exostosin1 and Exostosin2, or the HSPG core protein Glypican5, we show that Shh accumulates around its source cells when they are surrounded by cells that have a mutated ECM. This accumulation of Shh is correlated with an increased noncell autonomous Shh response. Our results support a model in which Shh presented on the cell surface accumulates at or near ECM that lacks HSPGs, possibly due to the absence of these Shh sequestering molecules.
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