Bass Mark D, Morgan Mark R, Humphries Martin J
Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.
Sci Signal. 2009 Mar 31;2(64):pe18. doi: 10.1126/scisignal.264pe18.
The syndecan transmembrane proteoglycans synergize with receptors for extracellular matrix molecules and growth factors to initiate cytoplasmic signals in response to a range of extracellular stimuli. Syndecans influence a wide range of physiological processes, but their contribution is most apparent during wound repair. Aspects of syndecan biology that have attracted research interest include extracellular matrix binding, outside-to-inside plasma membrane signal propagation, activation of cytoplasmic signals, and shedding of the syndecan extracellular domain, but the mechanisms by which syndecan cytoplasmic signals modulate extracellular function remain largely unresolved. Hayashida et al. have now discovered that association between an endocytic regulator, Rab5, and the syndecan-1 cytoplasmic domain controlled the shedding of the syndecan-1 extracellular domain. The work describes a mechanistic investigation into inside-to-outside syndecan signaling and highlights several gaps in our understanding of the relation between cell-surface receptors and proteases. In this Perspective, we summarize the current understanding of receptor interplay and identify the challenges that face investigators of adhesion- and growth factor-dependent signaling.
多功能蛋白聚糖跨膜蛋白聚糖与细胞外基质分子和生长因子的受体协同作用，以响应一系列细胞外刺激引发细胞质信号。多功能蛋白聚糖影响广泛的生理过程，但其作用在伤口修复过程中最为明显。引起研究兴趣的多功能蛋白聚糖生物学方面包括细胞外基质结合、从外向内的质膜信号传导、细胞质信号的激活以及多功能蛋白聚糖细胞外结构域的脱落，但多功能蛋白聚糖细胞质信号调节细胞外功能的机制仍 largely 未得到解决。Hayashida 等人现在发现，一种内吞调节因子 Rab5 与多功能蛋白聚糖 -1 细胞质结构域之间的关联控制了多功能蛋白聚糖 -1 细胞外结构域的脱落。这项工作描述了对从内向外的多功能蛋白聚糖信号传导的机制研究，并突出了我们在理解细胞表面受体与蛋白酶之间关系方面的几个差距。在这篇观点文章中，我们总结了目前对受体相互作用的理解，并确定了依赖黏附因子和生长因子信号传导的研究人员所面临的挑战。
