Zehe Christoph, Engling André, Wegehingel Sabine, Schäfer Tobias, Nickel Walter
Heidelberg University Biochemistry Center (BZH), Im Neuenheimer Feld 328, 69120 Heidelberg, Germany.
Proc Natl Acad Sci U S A. 2006 Oct 17;103(42):15479-84. doi: 10.1073/pnas.0605997103. Epub 2006 Oct 9.
FGF-2 is an unconventionally secreted lectin that transmits proangiogenic signals through a ternary complex with high-affinity FGF receptors and heparan sulfate proteoglycans (HSPGs). Although FGF-2 signal transduction is understood in great detail, its mechanism of release from cells, which is independent of the classical secretory pathway, remains elusive. To test the hypothesis that FGF-2 secretion is linked to its cell-surface ligands, we studied FGF-2 release using mutants defective for HSPG binding and cells with impaired HSPG biosynthesis. Here, we report that a functional interaction between FGF-2 and HSPGs is required for net export of FGF-2 from mammalian cells. FGF-2 release requires extracellular, membrane-proximal HSPGs. We propose that extracellular HSPGs form a molecular trap that drives FGF-2 translocation across the plasma membrane.
成纤维细胞生长因子2（FGF - 2）是一种非传统分泌的凝集素，它通过与高亲和力的FGF受体和硫酸乙酰肝素蛋白聚糖（HSPGs）形成三元复合物来传递促血管生成信号。尽管对FGF - 2信号转导有非常详细的了解，但其从细胞中释放的机制（独立于经典分泌途径）仍然不清楚。为了检验FGF - 2分泌与其细胞表面配体相关的假说，我们使用了HSPG结合缺陷的突变体和HSPG生物合成受损的细胞来研究FGF - 2的释放。在此，我们报告FGF - 2与HSPGs之间的功能性相互作用是FGF - 2从哺乳动物细胞净输出所必需的。FGF - 2的释放需要细胞外、膜近端的HSPGs。我们提出细胞外HSPGs形成一个分子陷阱，驱动FGF - 2穿过质膜进行转运。
