Peles E, Nativ M, Lustig M, Grumet M, Schilling J, Martinez R, Plowman G D, Schlessinger J
Sugen, Inc., Redwood City, CA 94063, USA.
EMBO J. 1997 Mar 3;16(5):978-88. doi: 10.1093/emboj/16.5.978.
Receptor protein tyrosine phosphatase beta (RPTPbeta) expressed on the surface of glial cells binds to the glycosylphosphatidylinositol (GPI)-anchored recognition molecule contactin on neuronal cells leading to neurite outgrowth. We describe the cloning of a novel contactin-associated transmembrane receptor (p190/Caspr) containing a mosaic of domains implicated in protein-protein interactions. The extracellular domain of Caspr contains a neurophilin/coagulation factor homology domain, a region related to fibrinogen beta/gamma, epidermal growth factor-like repeats, neurexin motifs as well as unique PGY repeats found in a molluscan adhesive protein. The cytoplasmic domain of Caspr contains a proline-rich sequence capable of binding to a subclass of SH3 domains of signaling molecules. Caspr and contactin exist as a complex in rat brain and are bound to each other by means of lateral (cis) interactions in the plasma membrane. We propose that Caspr may function as a signaling component of contactin, enabling recruitment and activation of intracellular signaling pathways in neurons. The binding of RPTPbeta to the contactin-Caspr complex could provide a mechanism for cell-cell communication between glial cells and neurons during development.
在神经胶质细胞表面表达的受体蛋白酪氨酸磷酸酶β（RPTPβ）与神经元细胞上糖基磷脂酰肌醇（GPI）锚定的识别分子接触蛋白结合，从而导致神经突生长。我们描述了一种新型接触蛋白相关跨膜受体（p190/Caspr）的克隆，该受体包含一系列与蛋白质-蛋白质相互作用有关的结构域。Caspr的胞外结构域包含一个亲环素/凝血因子同源结构域、一个与纤维蛋白原β/γ相关的区域、表皮生长因子样重复序列、神经连接蛋白基序以及在一种软体动物粘附蛋白中发现的独特PGY重复序列。Caspr的胞质结构域包含一个富含脯氨酸的序列，能够与信号分子的一类SH3结构域结合。Caspr和接触蛋白在大鼠脑中以复合物形式存在，并通过质膜中的侧向（顺式）相互作用彼此结合。我们提出，Caspr可能作为接触蛋白的信号成分发挥作用，从而在神经元中募集和激活细胞内信号通路。RPTPβ与接触蛋白-Caspr复合物的结合可能为发育过程中神经胶质细胞与神经元之间的细胞间通讯提供一种机制。
