Adams R H, Lohrum M, Klostermann A, Betz H, Püschel A W
Abteilung Neurochemie, Max-Planck-Institut für Hirnforschung, Deutschordenstr. 46, D-60528 Frankfurt/Main, Germany.
EMBO J. 1997 Oct 15;16(20):6077-86. doi: 10.1093/emboj/16.20.6077.
The semaphorins are a large group of cell surface and secreted proteins implicated in axonal pathfinding. Here we show that the secreted mouse semaphorin D (SemD) is synthesized as an inactive precursor (proSemD) and becomes repulsive for sensory and sympathetic neurites upon proteolytic cleavage. ProSemD processing can be blocked completely by an inhibitor selective for furin-like endoproteases or mutagenesis of three conserved dibasic cleavage sites. Its C-terminal pro-peptide contains a processing signal that is essential for SemD to acquire its full repulsive activity. SemD processing is regulated during the embryonic development of the mouse and determines the magnitude of its repulsive activity. Similarly to SemD, the secreted semaphorins SemA and SemE display repulsive properties that are regulated by processing. Our data suggest that differential proteolytic processing determines the repulsive potency of secreted semaphorins and implicate proteolysis as an important regulatory mechanism in axonal pathfinding.
信号素是一大类与轴突导向有关的细胞表面蛋白和分泌蛋白。我们在此表明，分泌型小鼠信号素D（SemD）最初以无活性前体（proSemD）形式合成，经蛋白水解切割后对感觉神经和交感神经轴突产生排斥作用。proSemD的加工过程可被一种对弗林蛋白酶样内切蛋白酶具有选择性的抑制剂或三个保守双碱性切割位点的诱变完全阻断。其C端前肽包含一个加工信号，该信号对于SemD获得其完全排斥活性至关重要。SemD的加工过程在小鼠胚胎发育过程中受到调控，并决定其排斥活性的大小。与SemD类似，分泌型信号素SemA和SemE也表现出受加工调控的排斥特性。我们的数据表明，差异蛋白水解加工决定了分泌型信号素的排斥效力，并暗示蛋白水解是轴突导向中的一种重要调控机制。
