LOTUS suppresses axon growth inhibition by blocking interaction between Nogo receptor-1 and all four types of its ligand
LOTUS suppresses axon growth inhibition by blocking interaction between Nogo receptor-1 and all four types of its ligand
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DOI：
10.1016/j.mcn.2014.07.001
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发表时间：
2014-07-01
影响因子：
3.5
通讯作者：
Takei, Kohtaro
中科院分区：
文献类型：
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作者：
Kurihara, Yuji;Iketani, Masumi;Takei, Kohtaro
轴突生长抑制剂，如 Nogo 蛋白、髓磷脂相关糖蛋白 (MAG)、少突胶质细胞髓磷脂糖蛋白 (OMgp) 和 B 淋巴细胞刺激剂 (BLyS) 通常与 Nogo 受体 1 (NgR1) 结合，导致成人中枢神经系统受损后功能恢复受到极大限制。最近，我们发现侧嗅道引导物质（LOTUS）拮抗 NgR1 介导的 Nogo 信号传导。然而，LOTUS 与其他三个配体结合时是否对 NgR1 产生拮抗作用尚未确定。在 COS7 细胞中，LOTUS 与 NgR1 一起过表达可阻断 MAG、OMgp 和 BLyS 与 NgR1 的结合。在培养的背根神经节神经元中，内源性 LOTUS 仅微弱表达，LOTUS 的过度表达抑制了这三种 NgR1 配体诱导的生长锥塌陷和神经突生长抑制。 LOTUS 抑制了培养的嗅球神经元中 NgR1 配体诱导的生长锥塌陷，这些神经元内源性表达 LOTUS。在 Lotus 缺陷小鼠中，NgR1 配体诱导生长锥塌陷。这些数据表明，当 LOTUS 与所有四种已知的 NgR1 配体结合时，LOTUS 可作为 NgR1 的有效内源性拮抗剂，这提高了 LOTUS 可能保护神经元免受 NgR1 介导的轴突生长抑制的可能性，从而可能作为 NgR1 的有效抑制剂促进神经元再生。 (C) 2014 Elsevier Inc. 保留所有权利。
Axon growth inhibitors such as Nogo proteins, myelin-associated glycoprotein (MAG), oligodendrocyte myelin glycoprotein (OMgp), and B lymphocyte stimulator (BLyS) commonly bind to Nogo receptor-1 (NgR1), leading to enormous restriction of functional recovery after damage to the adult central nervous system. Recently, we found that lateral olfactory tract usher substance (LOTUS) antagonizes NgR1-mediated Nogo signaling. However, whether LOTUS exerts antagonism of NgR1 when bound by the other three ligands has not been determined. Overexpression of LOTUS together with NgR1 in COS7 cells blocked the binding of MAG, OMgp, and BLyS to NgR1. In cultured dorsal root ganglion neurons in which endogenous LOTUS is only weakly expressed, overexpression of LOTUS suppressed growth cone collapse and neurite outgrowth inhibition induced by these three NgR1 ligands. LOTUS suppressed NgR1 ligand-induced growth cone collapse in cultured olfactory bulb neurons, which endogenously express LOTUS. Growth cone collapse was induced by NgR1 ligands in lotus-deficient mice. These data suggest that LOTUS functions as a potent endogenous antagonist for NgR1 when bound by all four known NgR1 ligands, raising the possibility that LOTUS may protect neurons from NgR1-mediated axonal growth inhibition and thereby may be useful for promoting neuronal regeneration as a potent inhibitor of NgR1. (C) 2014 Elsevier Inc. All rights reserved.