The genes encoding growth cone repulsive molecules

编码生长锥排斥分子的基因

基本信息

批准号：
08044282
负责人：
FURUYAMA Shinobu
金额：
$ 15.62万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

Axon pathfinding during neural development depends on both attractive and repulsive guidance signals.The collapsins/semaphorins are a large family of structurally distinct secreted and transmembrane proteins characterized by the presence of a conserved semaphorin domain (sema domain) of about 500 amino acids at their amino acid termini. Chick collapsin-1 (coll-1) and its mammalian homolog semaphorin D (semD) functions in vitro as a collapsing factor for gorwth cones of sensory and sympathetic neurons, and also acts as a selective chemorepellent for subpopulations of spinal and cranial, sensory and motor axons. However no or little is known on the other semaphorins. In this research, we have identified two transmembrane semaphorins, M-semaF and M-semaG,and one secreted semaphorins, M-semak. Their expression, protein distribution, and functions were analyzed in this reserach project. The mRNAs for M-semaF and M-semaG were in the neuronal tissues and and non-neuronal tissues. M-semaF expression was prominent in the immature brain and spinal cord, while M-semaG expression was found in both embryos and postnatal animals. The latter one was strongly expressed in the immune tissues such as the thymus as well as in the neuronal tissues. These results suggest that M-semaG play an important role in the immune system as well as in the nervous system. We also produced antibodies to these semaphorins, and studied the localization of the proteins in the tissues. The proteins were principally found in axons and at low levels in the neuronal cell bodies. We also confirmed the strong expression for M-SemaG on the surface of T1ymphocytes, suggesting it is involved the the interaction of T and B cells. We developed the biological assays, such as the adhesion, growth cone collapse, and coculture assays. We will furher study using those and additional assays what functions these molecules involved in and what molecules are the counter receptors for these molecules.

神经发育过程中的轴突寻路取决于吸引和排斥的引导信号。塌陷蛋白/信号蛋白是一个结构不同的分泌和跨膜蛋白大家族，其特征是在其氨基上存在约 500 个氨基酸的保守信号蛋白结构域（sema 结构域）酸末端。 Chick collapsin-1 (coll-1) 及其哺乳动物同源信号蛋白 D (semD) 在体外作为感觉和交感神经元生长锥的塌陷因子起作用，并且还作为脊髓和颅、感觉和神经亚群的选择性化学排斥剂。运动轴突。然而，对其他信号蛋白却一无所知或知之甚少。在这项研究中，我们鉴定了两种跨膜信号蛋白，M-semaF 和 M-semaG，以及一种分泌性信号蛋白，M-semak。本研究项目对它们的表达、蛋白质分布和功能进行了分析。 M-semaF 和 M-semaG 的 mRNA 存在于神经元组织和非神经元组织中。 M-semaF 表达在未成熟的大脑和脊髓中显着，而 M-semaG 表达在胚胎和出生后动物中均发现。后一种在胸腺等免疫组织以及神经元组织中强烈表达。这些结果表明 M-semaG 在免疫系统和神经系统中发挥着重要作用。我们还生产了这些信号蛋白的抗体，并研究了这些蛋白质在组织中的定位。这些蛋白质主要存在于轴突中，并且在神经元细胞体中含量较低。我们还证实了M-SemaG在T1淋巴细胞表面的强表达，表明它涉及T细胞和B细胞的相互作用。我们开发了生物测定法，例如粘附、生长锥塌陷和共培养测定法。我们将使用这些和其他分析进一步研究这些分子参与哪些功能以及哪些分子是这些分子的反受体。