F-spondin regulates neuronal survival through activation of disabled-1 in the chicken ciliary ganglion
F-spondin regulates neuronal survival through activation of disabled-1 in the chicken ciliary ganglion
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DOI：
10.1016/j.mcn.2010.12.001
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发表时间：
2011-02-01
影响因子：
3.5
通讯作者：
Unsicker, K.
中科院分区：
文献类型：
--
作者：
Peterziel, H.;Sackmann, T.;Unsicker, K.
细胞外膜相关蛋白F-pondin参与细胞-基质和细胞-细胞间的黏附，并在轴突通路中发挥重要作用。我们在这里报道了F-Spinin在鸡胚胎睫状神经节(CG)的非神经细胞中的表达，并有力地促进了培养的CG神经元的存活。利用F-响应蛋白的缺失结构，我们发现氨基末端的Reelin/Spinin结构域与凝血酶反应蛋白1型重复序列(TSR)6协同作用，TSR 6是一个具有功能的转化生长因子β激活结构域。在OVO处理中，针对Reelin/pondin结构域或TSR结构域的封闭抗体可导致程序性细胞死亡时CG神经元的凋亡率增加，与对照组相比约有30%的神经元丢失。Reelin/pondin结构域受体-APP及其下游信号分子DISABLED-1在CG神经元中表达。F-响应蛋白诱导Disable-1的快速磷酸化。此外，阻断中央APP结构域和干扰失活的-1信号都破坏了F-响应蛋白促进生存的作用。综上所述，我们的数据表明，F-Spinin可以通过涉及Reelin/Spinin和TSR结构域的机制促进神经元存活。(C)2010 Elsevier Inc.保留所有权利。
The extracellular membrane-associated protein F-spondin has been implicated in cell-matrix and cell-cell adhesion and plays an important role in axonal pathfinding. We report here that F-spondin is expressed in non-neuronal cells in the embryonic chicken ciliary ganglion (CG) and robustly promotes survival of cultured CG neurons. Using deletion constructs of F-spondin we found that the amino-terminal Reelin/Spondin domain cooperates with thrombospondin type 1 repeat (TSR) 6, a functional TGF beta-activation domain. In ovo treatment with blocking antibodies raised against the Reelin/Spondin domain or the TSR-domains caused increased apoptosis of CG neurons during the phase of programmed cell death and loss of about 30% of the neurons compared to controls. The Reelin/Spondin domain receptor - APP and its downstream signalling molecule disabled-1 are expressed in CG neurons. F-spondin induced rapid phosphorylation of disabled-1. Moreover, both blocking the central APP domain and interference with disabled-1 signalling disrupted the survival promoting effect of F-spondin. Taken together, our data suggest that F-spondin can promote neuron survival by a mechanism involving the Reelin/Spondin and the TSR domains. (C) 2010 Elsevier Inc. All rights reserved.