The chemorepulsive activity of secreted semaphorins is regulated by furin-dependent proteolytic processing
The chemorepulsive activity of secreted semaphorins is regulated by furin-dependent proteolytic processing
复制标题
DOI：
10.1093/emboj/16.20.6077
复制
发表时间：
1997-10-15
期刊：
影响因子：
11.4
通讯作者：
Puschel, AW
中科院分区：
文献类型：
--
作者：
Adams, RH;Lohrum, M;Puschel, AW
信号蛋白是一大类与轴突寻路有关的细胞表面和分泌蛋白。在这里，我们表明，分泌的小鼠信号蛋白 D (SemD) 是作为无活性前体 (proSemD) 合成的，并且在蛋白水解裂解后变得对感觉和交感神经突具有排斥性，ProSemD 加工可以通过对弗林蛋白酶样内切蛋白酶选择性的抑制剂或三个保守二碱基裂解位点的诱变来完全阻断。其 C 端前肽包含一个处理信号，该信号对于 SemD 获得其完全排斥活性至关重要。 SemD 处理在小鼠胚胎发育过程中受到调节，并决定其排斥活性的强度。与 SemD 类似，分泌型信号蛋白 SemA 和 SemE 显示出受加工调节的排斥特性。我们的数据表明，差异蛋白水解加工决定了分泌型信号蛋白的排斥效力，并暗示蛋白水解是轴突寻路的重要调节机制。
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.