Reception of Slit requires only the chondroitin-sulphate-modified extracellular domain of Syndecan at the target cell surface
Reception of Slit requires only the chondroitin-sulphate-modified extracellular domain of Syndecan at the target cell surface
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DOI：
10.1073/pnas.0901148106
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发表时间：
2009-07-21
影响因子：
11.1
通讯作者：
Vorbrueggen, Gerd
中科院分区：
文献类型：
--
作者：
Chanana, Bhavna;Steigemann, Patrick;Vorbrueggen, Gerd
多配体蛋白聚糖（Syndecan，Sdc）是一种保守的跨膜硫酸乙酰肝素蛋白聚糖（HSPG），其胞外结构域具有额外的硫酸软骨素（chondroitin sulfate，CS）修饰。在脊椎动物中，Sdc的这种胞外结构域脱落并充当细胞通讯事件的可溶性效应物，其胞质结构域参与维持上皮完整性所需的胞内信号传导。在果蝇中，Sdc已被证明是必需的Slit信号依赖性轴突和肌管的指导在中枢神经系统的发展和肌肉图案的形成。我们报告说，Sdc的行为在一个细胞自主的方式在狭缝接收细胞，其膜锚定的胞外结构域是足以介导狭缝信号。Sdc的活性可以被人类同源物hsdc 2所取代。然而，HSPG Dally样蛋白（Dlp），其在其胞外结构域缺乏CS修饰，只能部分取代Sdc功能，并且其活性不限于Slit靶细胞。我们的研究结果表明，Sdc和Dlp的行为在轴突和肌管指导的合作，但非冗余的方式。我们建议，Dlp，它缺乏CS的修改，参与转移的Slit从其网站的表达到靶细胞，CS-修改的Sdc浓度和提出的配体。
Syndecan (Sdc) is a conserved transmembrane heparan sulfate proteoglycan (HSPG) bearing additional chondroitin sulfate (CS) modifications on its extracellular domain. In vertebrates, this extracellular domain of Sdc is shed and acts as a soluble effector of cellular communication events, and its cytoplasmic domain participates in intracellular signaling needed to maintain epithelial integrity. In Drosophila, Sdc has been shown to be necessary for Slit signaling-dependent axon and myotube guidance during CNS development and muscle pattern formation. We report that Sdc acts in a cell-autonomous manner in Slit-receiving cells and that its membrane-anchored extracellular domain is sufficient to mediate Slit signaling. Sdc activity can be replaced by the human homolog hsdc2. However, the HSPG Dally-like protein (Dlp), which lacks CS modifications at its extracellular domain, can only partially substitute for Sdc function, and its activity is not restricted to the Slit target cells. Our results suggest that Sdc and Dlp act in a cooperative but nonredundant fashion in axon and myotube guidance. We propose that Dlp, which lacks CS modifications, participates in the transfer of Slit from its site of expression to the target cells, where CS-modified Sdc concentrates and presents the ligand.