Proteolysis and membrane capture of F-spondin generates combinatorial guidance cues from a single molecule
Proteolysis and membrane capture of F-spondin generates combinatorial guidance cues from a single molecule
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F-spondin 的蛋白水解和膜捕获从单个分子产生组合引导线索
作者：
S. Zisman;K. Marom;O. Avraham;L. Rinsky;Uri Gai;Gilit Kligun;Vered Tzarfaty;Tatsuo Suzuki;A. Klar
神经元网络的形成由有限数量的引导分子控制，但它非常复杂。引导分子及其受体的翻译后修饰增加了引导线索的复杂性。我们在此报告，底板引导分子 F-spondin 的裂解产生两个功能相反的片段：沉积在底板细胞膜中的短程排斥蛋白和在基底膜处积累的粘附蛋白。它们的协调活动，分别充当短程排斥剂和允许的短程引诱剂，将连合轴突收缩到底板细胞下方的基底膜。我们进一步证明，F-spondin 抑制片段的排斥活性需要由脂蛋白受体相关蛋白 (LRP) 受体载脂蛋白 E 受体 2、LRP2/巨蛋白和 LRP4 呈递，这些受体在底板中表达。因此，蛋白水解和膜相互作用协调源自单一引导线索的组合引导信号传导。
The formation of neuronal networks is governed by a limited number of guidance molecules, yet it is immensely complex. The complexity of guidance cues is augmented by posttranslational modification of guidance molecules and their receptors. We report here that cleavage of the floor plate guidance molecule F-spondin generates two functionally opposing fragments: a short-range repellent protein deposited in the membrane of floor plate cells and an adhesive protein that accumulates at the basement membrane. Their coordinated activity, acting respectively as a short-range repellant and a permissive short-range attractant, constricts commissural axons to the basement membrane beneath the floor plate cells. We further demonstrate that the repulsive activity of the inhibitory fragment of F-spondin requires its presentation by the lipoprotein receptor–related protein (LRP) receptors apolipoprotein E receptor 2, LRP2/megalin, and LRP4, which are expressed in the floor plate. Thus, proteolysis and membrane interaction coordinate combinatorial guidance signaling originating from a single guidance cue.