Gobron S, Monnerie H, Meiniel R, Creveaux I, Lehmann W, Lamalle D, Dastugue B, Meiniel A
Laboratoire de Biochimie Médicale, Institut National de la Santé et de la Recherche Médicale, Faculté de Médecine, Clermont-Ferrand, France.
J Cell Sci. 1996 May;109 ( Pt 5):1053-61. doi: 10.1242/jcs.109.5.1053.
A number of cues are known to influence neuronal development including growth factors, cell-adhesion molecules, components of the extracellular matrix and guidance molecules. In this study, we present molecular and functional evidence that SCO-spondin, a novel relative of the thrombospondin family, could also be involved in neuronal development by modulating cell aggregative mechanisms. SCO-spondin corresponds to glycoproteins secreted by the subcommissural organ (SCO), an ependymal differentiation of the vertebrate brain located at the entrance to the Sylvian aqueduct. A cDNA clone of 2.6 kb, isolated from a bovine SCO cDNA library, was shown to be specifically and highly expressed in the bovine SCO by in situ hybridization and was subsequently sequenced. Analysis of the deduced amino acid sequence reveals the presence of four conserved domains known as thrombospondin (TSP) type I repeats. To account for the homology with thrombospondins and F-spondin, this secreted glycoprotein was called SCO-spondin. Two potent binding sites to glycosaminoglycan (BBXB) and to cytokine (TXWSXWS) are also found in the TSP type I repeats. The deduced amino acid sequence exhibits three other conserved domains called low density lipoprotein (LDL) receptor type A repeats. The possibility of SCO-spondin involvement in neuronal development as a component of the extracellular matrix is discussed regarding these molecular features. The idea of a modulation of cell-cell and/or cell-matrix interaction is further supported by the anti-aggregative effect observed on cultured neuronal cells of material solubilized from Reissner's fiber. That Reissner's fiber, the condensed secretory product of the SCO present along the whole spinal cord can be a potent morphogenetical structure is an important concept for the analysis of the molecular mechanisms leading to spinal cord differentiation.
已知许多线索会影响神经元发育，包括生长因子、细胞黏附分子、细胞外基质成分和导向分子。在本研究中，我们提供了分子和功能证据，表明血小板反应蛋白家族的新成员SCO-spondin也可能通过调节细胞聚集机制参与神经元发育。SCO-spondin对应于由连合下器官（SCO）分泌的糖蛋白，SCO是位于大脑导水管入口处的脊椎动物脑的室管膜分化结构。从牛SCO cDNA文库中分离出一个2.6 kb的cDNA克隆，通过原位杂交显示其在牛SCO中特异性高表达，随后进行了测序。对推导的氨基酸序列分析揭示了存在四个称为血小板反应蛋白（TSP）I型重复序列的保守结构域。为了解释与血小板反应蛋白和F-spondin的同源性，这种分泌性糖蛋白被称为SCO-spondin。在TSP I型重复序列中还发现了两个与糖胺聚糖（BBXB）和细胞因子（TXWSXWS）的强结合位点。推导的氨基酸序列还显示出另外三个保守结构域，称为低密度脂蛋白（LDL）受体A型重复序列。基于这些分子特征，讨论了SCO-spondin作为细胞外基质成分参与神经元发育的可能性。从Reissner纤维中溶解的物质对培养的神经元细胞具有抗聚集作用，这进一步支持了细胞-细胞和/或细胞-基质相互作用受到调节的观点。Reissner纤维是沿整个脊髓存在的SCO的浓缩分泌产物，它可能是一种强大的形态发生结构，这是分析导致脊髓分化的分子机制的一个重要概念。
