Mammalian septin function in hemostasis and beyond
Mammalian septin function in hemostasis and beyond
复制标题
DOI：
10.1177/153537020422901105
复制
发表时间：
2004-12-01
影响因子：
3.2
通讯作者：
Ware, J
中科院分区：
文献类型：
--
作者：
Martinez, C;Ware, J
近年来，人们对哺乳动物脓毒症蛋白的生物学兴趣产生了兴趣。 septin 家族最初在 20 世纪 70 年代被认为对酵母出芽至关重要，现在被认为可以从酵母延伸到人类，并与从胞质分裂到囊泡运输等多种事件相关。脓毒症的一个新兴主题是它们存在于发生活性膜或细胞质分配的位点。在这里，我们简要回顾了哺乳动物脓蛋白家族，并重点关注了一种原型人类和小鼠脓蛋白，称为 SEPT5，它在大脑、心脏和巨核细胞中表达。神经生物学实验室的工作已将 SEPT5 与神经元的胞吐复合体联系起来，这表明 SEPT5 调节神经递质的释放。神经递质释放和血小板释放反应之间存在惊人的相似性，这是血小板对血管损伤反应的关键步骤。我们实验室的工作已经对含有 SEPT5 靶向缺失的小鼠的血小板表型进行了表征。最引人注目的是，来自 SEPT5（无效）动物的血小板响应阈下水平的激动剂聚集并释放颗粒内容物。因此，SEPT5 缺陷小鼠的特征将 SEPT5 与血小板胞吐过程联系起来，因此说明它是调节血小板功能的重要蛋白质。最近的数据表明，血小板含有多种不同的脓毒蛋白，并组装形成大分子脓毒蛋白复合物。小鼠血小板提供了一个实验框架来定义隔膜在止血中的功能，对神经生物学及其他领域具有重要意义。
Interest in the biology of mammalian septin proteins has undergone a birth in recent years. Originally identified as critical for yeast budding throughout the 1970s, the septin family is now recognized to extend from yeast to humans and is associated with a variety of events ranging from cytokinesis to vesicle trafficking. An emerging theme for septins is their presence at sites where active membrane or cytoplasmic partitioning is occurring. Here, we briefly review the mammalian septin protein family and focus on a prototypic human and mouse septin, termed SEPT5, that is expressed in the brain, heart, and megakaryocytes. Work from neurobiology laboratories has linked SEPT5 to the exocytic complex of neurons, with implications that SEPT5 regulates neurotransmitter release. Striking similarities exist between neurotransmitter release and the platelet-release reaction, which is a critical step in platelet response to vascular injury. Work from our laboratory has characterized the platelet phenotype from mice containing a targeted deletion of SEPT5. Most strikingly, platelets from SEPT5(null) animals aggregate and release granular contents in response to subthreshold levels of agonists. Thus, the characterization of a SEPT5-deficient mouse has linked SEPT5 to the platelet exocytic process and, as such, illustrates it as an important protein for regulating platelet function. Recent data suggest that platelets contain a wide repertoire of different septin proteins and assemble to form macromolecular septin complexes. The mouse platelet provides an experimental framework to define septin function in hemostasis, with implications for neurobiology and beyond.