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首页> 外文期刊>Development >A translational block to HSPG synthesis permits BMP signaling in the early Drosophila embryo.
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A translational block to HSPG synthesis permits BMP signaling in the early Drosophila embryo.

机译：HSPG合成的翻译阻滞允许果蝇早期胚胎中的BMP信号传导。

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摘要

Heparan sulfate proteoglycans (HSPGs) are extracellular macromolecules found on virtually every cell type in eumetazoans. HSPGs are composed of a core protein covalently linked to glycosaminoglycan (GAG) sugar chains that bind and modulate the signaling efficiency of many ligands, including Hedgehog (Hh), Wingless (Wg) and Bone morphogenetic proteins (BMPs). Here, we show that, in Drosophila, loss of HSPGs differentially affects embryonic Hh, Wg and BMP signaling. We find that a stage-specific block to GAG synthesis prevents HSPG expression during establishment of the BMP activity gradient that is crucial for dorsal embryonic patterning. Subsequently, GAG synthesis is initiated coincident with the onset of Hh and Wg signaling which require HSPGs. This temporal regulation is achieved by the translational control of HSPG synthetic enzymes through internal ribosome entry sites (IRESs). IRES-like features are conserved in GAG enzyme transcripts from diverse organisms, suggesting that this represents a novel evolutionarily conserved mechanism for regulating GAG synthesis and modulating growth factor activity.
机译：硫酸乙酰肝素蛋白聚糖（HSPG）是在全美杜鹃中几乎每种细胞类型上都发现的细胞外大分子。 HSPG由共价连接至糖胺聚糖（GAG）糖链的核心蛋白组成，该糖蛋白结合并调节许多配体的信号传导效率，包括刺猬（Hh），无翅（Wg）和骨形态发生蛋白（BMP）。在这里，我们表明，在果蝇中，HSPG的丢失会差异性地影响胚胎Hh，Wg和BMP信号传导。我们发现，GAG合成的特定阶段阻滞阻止了BMP活性梯度建立过程中的HSPG表达，而BMP活性梯度对于背侧胚胎形成至关重要。随后，GAG合成与需要HSPG的Hh和Wg信号的发动同时开始。通过内部核糖体进入位点（IRESs）对HSPG合成酶的翻译控制，可以实现这种时间调节。类似于IRES的特征在来自多种生物的GAG酶转录物中是保守的，表明这代表了一种调节GAG合成和调节生长因子活性的新型进化保守机制。

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