Monnerie H, Dastugue B, Meiniel A
INSERM U 384, Faculté de Médecine, 28 Place Henri-Dunant, BP n degrees38, F-63001 Clermont-Ferrand cedex, France.
Cell Tissue Res. 1998 Sep;293(3):407-18. doi: 10.1007/s004410051132.
SCO-spondin is a newly identified protein, strongly expressed in the subcommissural organ (SCO), an ependymal differentiation of the brain. When secreted into the cerebrospinal fluid at the entrance to the Sylvian aqueduct, it condenses and forms Reissner's fiber. Several conserved domains have previously been characterizedin SCO-spondin, e.g., thrombospondin type 1 repeats (TSRs), low-density lipoprotein receptor (LDLr) type A repeats, and epidermal-growth-factor-like domains, which are potent sites of protein-protein interaction. To clarify the role of this protein on neuronal development, we have tested the effect of oligopeptides, the sequences of which include highly conserved amino acids of TSRs, LDLr type A repeats and a potent site of attachment to proteoglycan, on cortical and spinal-cord neurons in primary cell cultures. One of these peptides (WSGWSSCSRSCG), corresponding to a SCO-spondin TSR sequence, markedly increases adhesivity and neuritic outgrowth of cortical neurons and induces an opposite effect on cortical and spinal-cord neuronal aggregation. These effects are specific, as no response is observed with the scrambled sequence of this peptide. Another peptide (WGPCSVSCG) is only slightly active on adhesivity and neuritic outgrowth of cortical neurons and has no effect on spinal-cord neurons. Peptides derived from other conserved domains of SCO-spondin are not effective under our experimental conditions. Thus, SCO-spondin may be responsible for at least a part of the effects previously observed on neuronal cells cultured in the presence of Reissner's fiber. In addition, SCO-spondin seems to interfere with neuronal development and/or axonal guidance during ontogenesis of the central nervous system in modulating side-to-side interactions and neuritic outgrowth.
SCO-spondin是一种新发现的蛋白质，在脑导水管周围器官（SCO）中强烈表达，SCO是脑的一种室管膜分化结构。当它在中脑导水管入口处分泌到脑脊液中时，会凝聚形成赖氏纤维。先前已在SCO-spondin中鉴定出几个保守结构域，例如血小板反应蛋白1型重复序列（TSRs）、低密度脂蛋白受体（LDLr）A型重复序列以及表皮生长因子样结构域，这些都是蛋白质-蛋白质相互作用的重要位点。为了阐明这种蛋白质在神经元发育中的作用，我们测试了一些寡肽的作用，这些寡肽的序列包含TSRs、LDLr A型重复序列的高度保守氨基酸以及与蛋白聚糖结合的一个有效位点，对原代细胞培养中的皮质神经元和脊髓神经元的影响。其中一种肽（WSGWSSCSRSCG），对应于SCO-spondin的TSR序列，显著增加了皮质神经元的黏附性和神经突生长，并对皮质和脊髓神经元聚集产生相反的影响。这些作用是特异性的，因为该肽的 scrambled 序列没有观察到反应。另一种肽（WGPCSVSCG）对皮质神经元的黏附性和神经突生长只有轻微活性，对脊髓神经元没有影响。在我们的实验条件下，源自SCO-spondin其他保守结构域的肽没有效果。因此，SCO-spondin可能至少对先前在存在赖氏纤维的情况下培养的神经元细胞上观察到的部分效应负责。此外，SCO-spondin似乎在中枢神经系统个体发生过程中干扰神经元发育和/或轴突导向，调节侧向相互作用和神经突生长。
