Lai K O, Fu W Y, Ip F C, Ip N Y
Department of Biology, Hong Kong University of Science and Technology, China.
Mol Cell Neurosci. 1998 May;11(1-2):64-76. doi: 10.1006/mcne.1998.0666.
Neurotrophins have been demonstrated to play important roles in the development and functioning of the nervous system. This family of proteins consists of four homologous members in mammals: NGF, BDNF, NT-3, and NT-4/5. A new member, called NT-6, was recently cloned from the platyfish Xiphophorus maculatus. This protein shares closer structural relationship to NGF than the other neurotrophins, but contains a characteristic insertion of 22 amino acids that constituted the heparin-binding domain. Here we report the cloning of a novel neurotrophin from the fish Cyprinus carpio (carp), which shared about 66% amino acid identity to Xiphophorus NGF and NT-6. The neurotrophin, designated NT-7, possesses structural characteristics common to all known neurotrophins, such as the presence of six conserved cysteine residues and the flanking conserved sequences. In addition, there is an insertion of 15 amino acids at the position corresponding to that observed for NT-6. The neurotrophic activity of NT-7 was demonstrated by its ability to promote neurite outgrowth and neuronal survival of chick dorsal root ganglia. Phosphorylation assay of various Trk receptors overexpressed in fibroblasts suggested that NT-7 could activate TrkA but not TrkB or TrkC. Northern blot analysis revealed that NT-7 was predominantly expressed in peripheral tissues, though weak expression was also detected in the brain. Like NT-6, this novel neurotrophin might represent yet another NGF-like neurotrophin in lower vertebrates.
神经营养因子已被证明在神经系统的发育和功能中发挥重要作用。该蛋白家族在哺乳动物中由四个同源成员组成:神经生长因子(NGF)、脑源性神经营养因子(BDNF)、神经营养因子-3(NT-3)和神经营养因子-4/5(NT-4/5)。最近从剑尾鱼(Xiphophorus maculatus)中克隆出一个新成员,称为NT-6。与其他神经营养因子相比,该蛋白与NGF的结构关系更密切,但含有一个由22个氨基酸组成的特征性插入序列,构成了肝素结合结构域。在此,我们报告从鲤鱼(Cyprinus carpio)中克隆出一种新型神经营养因子,它与剑尾鱼NGF和NT-6的氨基酸同一性约为66%。这种神经营养因子被命名为NT-7,具有所有已知神经营养因子共有的结构特征,如存在六个保守的半胱氨酸残基和侧翼保守序列。此外,在与NT-6相应的位置有15个氨基酸的插入。NT-7的神经营养活性通过其促进鸡背根神经节神经突生长和神经元存活的能力得以证明。对在成纤维细胞中过表达的各种Trk受体进行磷酸化分析表明,NT-7可以激活TrkA,但不能激活TrkB或TrkC。Northern印迹分析显示,NT-7主要在外周组织中表达,尽管在脑中也检测到微弱表达。与NT-6一样,这种新型神经营养因子可能代表了低等脊椎动物中另一种类似NGF的神经营养因子。