Gennarini G, Cibelli G, Rougon G, Mattei M G, Goridis C
Centre d'Immunologie, Marseille, France.
J Cell Biol. 1989 Aug;109(2):775-88. doi: 10.1083/jcb.109.2.775.
Several members of the Ig superfamily are expressed on neural cells where they participate in surface interactions between cell bodies and processes. Their Ig domains are more closely related to each other than to Ig variable and constant domains and have been grouped into the C2 set. Here, we report the cloning and characterization of another member of this group, the mouse neuronal cell surface antigen F3. The F3 cDNA sequence contains an open reading frame that could encode a 1,020-amino acid protein consisting of a signal sequence, six Ig-like domains of the C2 type, a long premembrane region containing two segments that exhibit sequence similarity to fibronectin type III repeats and a moderately hydrophobic COOH-terminal sequence. The protein does not contain a typical transmembrane segment but appears to be attached to the membrane by a phosphatidylinositol anchor. Antibodies against the F3 protein recognize a prominent 135-kD protein in mouse brain. In fetal brain cultures, they stain the neuronal cell surface and, in cultures maintained in chemically defined medium, most prominently neurites and neurite bundles. The mouse f3 gene maps to band F of chromosome 15. The gene transcripts detected in the brain by F3 cDNA probes are developmentally regulated, the highest amounts being expressed between 1 and 2 wk after birth. The F3 nucleotide and deduced amino acid sequence show striking similarity to the recently published sequence of the chicken neuronal cell surface protein contactin. However, there are important differences between the two molecules. In contrast to F3, contactin has a transmembrane and a cytoplasmic domain. Whereas contactin is insoluble in nonionic detergent and is tightly associated with the cytoskeleton, about equal amounts of F3 distribute between buffer-soluble, nonionic detergent-soluble, and detergent-insoluble fractions. Among other neural cell surface proteins, F3 most resembles the neuronal cell adhesion protein L1, with 25% amino acid identity between their extracellular domains. Based on its structural similarity with known cell adhesion proteins of nervous tissue and with L1 in particular, we propose that F3 mediates cell surface interactions during nervous system development.
免疫球蛋白超家族的几个成员在神经细胞上表达，它们参与细胞体与突起之间的表面相互作用。它们的免疫球蛋白结构域彼此之间的关系比与免疫球蛋白可变区和恒定区的关系更为密切，并已被归入C2组。在此，我们报告了该组另一个成员——小鼠神经元细胞表面抗原F3的克隆和特性。F3 cDNA序列包含一个开放阅读框，可编码一个1020个氨基酸的蛋白质，该蛋白质由一个信号序列、六个C2型免疫球蛋白样结构域、一个长的前膜区域组成，该区域包含两个与纤连蛋白III型重复序列具有序列相似性的片段以及一个中等疏水性的COOH末端序列。该蛋白质不包含典型的跨膜片段，但似乎通过磷脂酰肌醇锚定附着于膜上。针对F3蛋白的抗体识别小鼠脑中一种突出的135-kD蛋白。在胎脑培养物中, 它们对神经元细胞表面进行染色，并且在化学限定培养基中培养的培养物中，最显著的是神经突和神经突束。小鼠f3基因定位于15号染色体的F带。用F3 cDNA探针在脑中检测到的基因转录物受到发育调控，出生后1至2周表达量最高。F3核苷酸和推导的氨基酸序列与最近发表的鸡神经元细胞表面蛋白contactin的序列显示出惊人的相似性。然而，这两种分子之间存在重要差异。与F3不同，contactin具有一个跨膜结构域和一个细胞质结构域。contactin不溶于非离子去污剂并与细胞骨架紧密相关，而约等量的F3分布在缓冲液可溶、非离子去污剂可溶和去污剂不溶部分之间。在其他神经细胞表面蛋白中，F3与神经元细胞粘附蛋白L1最为相似，它们的细胞外结构域之间具有25%的氨基酸同一性。基于其与神经组织已知细胞粘附蛋白特别是与L1的结构相似性，我们提出F3在神经系统发育过程中介导细胞表面相互作用。
