Section of Molecular Mechanisms of Glaucoma, Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-0606, USA.
J Biol Chem. 2012 Oct 26;287(44):37171-84. doi: 10.1074/jbc.M112.389916. Epub 2012 Aug 24.
Olfm1, a secreted highly conserved glycoprotein, is detected in peripheral and central nervous tissues and participates in neural progenitor maintenance, cell death in brain, and optic nerve arborization. In this study, we identified Olfm1 as a molecule promoting axon growth through interaction with the Nogo A receptor (NgR1) complex. Olfm1 is coexpressed with NgR1 in dorsal root ganglia and retinal ganglion cells in embryonic and postnatal mice. Olfm1 specifically binds to NgR1, as judged by alkaline phosphatase assay and coimmunoprecipitation. The addition of Olfm1 inhibited the growth cone collapse of dorsal root ganglia neurons induced by myelin-associated inhibitors, indicating that Olfm1 attenuates the NgR1 receptor functions. Olfm1 caused the inhibition of NgR1 signaling by interfering with interaction between NgR1 and its coreceptors p75NTR or LINGO-1. In zebrafish, inhibition of optic nerve extension by olfm1 morpholino oligonucleotides was partially rescued by dominant negative ngr1 or lingo-1. These data introduce Olfm1 as a novel NgR1 ligand that may modulate the functions of the NgR1 complex in axonal growth.
Olfm1 是一种分泌型高度保守糖蛋白,在周围和中枢神经系统组织中均有检测到,其参与神经祖细胞的维持、脑内细胞死亡和视神经分支。在这项研究中,我们发现 Olfm1 是一种通过与 Nogo A 受体(NgR1)复合物相互作用来促进轴突生长的分子。Olfm1 在胚胎期和出生后的小鼠背根神经节和视网膜神经节细胞中与 NgR1 共表达。Olfm1 通过碱性磷酸酶测定和共免疫沉淀实验被判断为特异性结合 NgR1。Olfm1 的添加抑制了髓鞘相关抑制剂诱导的背根神经节神经元生长锥塌陷,表明 Olfm1 减弱了 NgR1 受体功能。Olfm1 通过干扰 NgR1 与其核心受体 p75NTR 或 LINGO-1 之间的相互作用,引起 NgR1 信号的抑制。在斑马鱼中,olfm1 形态发生素寡核苷酸对视神经延伸的抑制作用部分被显性负性 ngr1 或 lingo-1 挽救。这些数据表明 Olfm1 是一种新型的 NgR1 配体,可能调节 NgR1 复合物在轴突生长中的功能。