Retrograde propagation of GDNF-mediated signals in sympathetic neurons
Retrograde propagation of GDNF-mediated signals in sympathetic neurons
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DOI：
10.1016/j.mcn.2004.06.001
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发表时间：
2004-10-01
影响因子：
3.5
通讯作者：
Ibáñez, CF
中科院分区：
文献类型：
--
作者：
Coulpier, M;Ibáñez, CF
胶质细胞源性神经营养因子（GDNF）家族配体是几种神经元亚群的靶源性营养因子。它们通过与GDNF家族受体α（GFR α）的特定成员结合并随后激活RET酪氨酸激酶受体来促进存活和神经突生长。本实验采用隔室化培养的交感神经元，研究GDNF逆行信号转导的机制。我们的研究结果表明GDNF受体RET和GFR α 1存在于两个细胞室，细胞体和远端轴突。GDNF加入到任一区室启动局部信号传导，包括RET及其下游效应子AKT和ERK 1/2的激活。此外，GDNF的远端轴突诱导逆行信号，导致神经元的生存和轴突生长。逆行信号传导与放射性标记的GDNF和GFR α 1的逆行转运以及细胞体中RET和AKT的激活有关，但与ERK 1/2无关。未观察到顺行信号传播或传输。我们的研究结果表明，逆行信号通过酪氨酸激酶受体在远端轴突启动的一般机制。(C)2004年爱思唯尔公司All rights reserved.
Glial cell line-derived neurotrophic factor (GDNF) family ligands are target-derived trophic factors for several neuronal subpopulations. They promote survival and neurite outgrowth through binding to specific members of the GDNF family receptor alpha (GFRalpha) and subsequent activation of the RET tyrosine kinase receptor. sing compartmentalized cultures of sympathetic neurons, we have studied the mechanism of GDNF retrograde signaling. Our results demonstrate the presence of GDNF receptors RET and GFRalpha1 in the two cellular compartments, cell bodies and distal axons. Addition of GDNF to either compartment initiated local signaling, including activation of RET and its downstream effectors AKT and ERK1/2. Addition of GDNF to distal axons induced a retrograde signal leading to neuronal survival and neurite outgrowth. Retrograde signaling was associated with retrograde transport of radiolabeled GDNF and GFRalpha1, as well as activation of RET and AKT, but not of ERK1/2, in cell bodies. No anterograde signal propagation or transport was observed. Our results suggest a general mechanism for retrograde signaling initiated at distal axons through tyrosine kinase receptors. (C) 2004 Elsevier Inc. All rights reserved.