The carboxyl-terminal region of Crtac1B/LOTUS acts as a functional domain in endogenous antagonism to Nogo receptor-1
The carboxyl-terminal region of Crtac1B/LOTUS acts as a functional domain in endogenous antagonism to Nogo receptor-1
复制标题
DOI：
10.1016/j.bbrc.2012.01.033
复制
发表时间：
2012-02-10
影响因子：
3.1
通讯作者：
Takei, Kohtaro
中科院分区：
文献类型：
--
作者：
Kurihara, Yuji;Arie, Yuko;Takei, Kohtaro
髓鞘衍生的轴突生长抑制剂，如Nog，与Nogo受体-1 （NgR1）结合，从而限制成人中枢神经系统损伤后轴突再生的作用。最近，我们发现软骨酸性蛋白- 1b (Crtac1B)/外侧嗅道诱导物质（LOTUS）与NgR1结合，并作为内源性NgR1拮抗剂发挥作用。为了研究LOTUS在NgR1拮抗中的功能域，利用LOTUS的缺失突变体进行了分析，发现LOTUS的羧基末端区域（UA/EC结构域）与NgR1结合。在COS7细胞中，与NgR1一起过表达的LOTUS的UA/EC片段使Nogo66与NgR1的结合消失。在培养的鸡背根神经节神经元中过表达UA/EC片段可抑制nogo66诱导的生长锥塌陷。这些发现表明UA/EC区是LOTUS的一个功能域，对NgR1起拮抗作用。(C) 2012爱思唯尔公司版权所有。
Myelin-derived axon growth inhibitors, such as Nog, bind to Nogo receptor-1 (NgR1) and thereby limit the action of axonal regeneration after injury in the adult central nervous system. Recently, we have found that cartilage acidic protein-1B (Crtac1B)/lateral olfactory tract usher substance (LOTUS) binds to NgR1 and functions as an endogenous NgR1 antagonist. To examine the functional domain of LOTUS in the antagonism to NgR1, analysis using the deletion mutants of LOTUS was performed and revealed that the carboxyl-terminal region (UA/EC domain) of LOTUS bound to NgR1. The UA/EC fragment of LOTUS overexpressed together with NgR1 in COS7 cells abolished the binding of Nogo66 to NgR1. Overexpression of the UA/EC fragment in cultured chick dorsal root ganglion neurons suppressed Nogo66-induced growth cone collapse. These findings suggest that the UA/EC region is a functional domain of LOTUS serving for an antagonistic action to NgR1. (C) 2012 Elsevier Inc. All rights reserved.