Localized regulation of axonal RanGTPase controls retrograde injury signaling in peripheral nerve.
Localized regulation of axonal RanGTPase controls retrograde injury signaling in peripheral nerve.
复制标题
DOI：
10.1016/j.neuron.2008.05.029
复制
发表时间：
2008-07-31
期刊：
影响因子：
16.2
通讯作者：
Fainzilber M
中科院分区：
文献类型：
--
作者：
Yudin D;Hanz S;Yoo S;Iavnilovitch E;Willis D;Gradus T;Vuppalanchi D;Segal-Ruder Y;Ben-Yaakov K;Hieda M;Yoneda Y;Twiss JL;Fainzilber M
外周感觉神经元通过激活输入依赖性逆行信号机制对轴突损伤作出反应。这一机制是如何监管的？在这里，我们表明，Ran GT及其相关效应子RanBP 1和RanGAP调节损伤轴突中importin信号复合物的形成。核RanGTP与细胞质RanGDP的梯度被认为是真核细胞组织的基础。令人惊讶的是，我们在坐骨神经轴浆中发现RanGTP，远离神经元细胞体和细胞核，并与动力蛋白和importin α相关。损伤后，RanBP 1的局部翻译刺激RanGTP从输入蛋白解离并随后水解，从而允许新合成的输入蛋白β与输入蛋白α和动力蛋白结合。在轴突损伤部位的RanGTP水解或RanBP 1阻断的扰动降低了神经元条件性损伤反应。因此，神经元采用Ran调节的局部机制来控制外周神经中的逆行损伤信号传导。
Peripheral sensory neurons respond to axon injury by activating an importin-dependent retrograde signaling mechanism. How is this mechanism regulated? Here we show that Ran GTPase and its associated effectors RanBP1 and RanGAP regulate the formation of importin signaling complexes in injured axons. A gradient of nuclear RanGTP versus cytoplasmic RanGDP is thought to be fundamental for the organization of eukaryotic cells. Surprisingly, we find RanGTP in sciatic nerve axoplasm, distant from neuronal cell bodies and nuclei, and in association with dynein and importin α. Following injury, localized translation of RanBP1 stimulates RanGTP dissociation from importins and subsequent hydrolysis, thereby allowing binding of newly synthesized importin β to importin α and dynein. Perturbation of RanGTP hydrolysis or RanBP1 blockade at axonal injury sites reduces the neuronal conditioning lesion response. Thus, neurons employ localized mechanisms of Ran regulation to control retrograde injury signaling in peripheral nerve.
登录
查看更多内容
影响因子：
16.2
作者：
Jacobson, C;Schnapp, B;Banker, GA
通讯作者：
Banker, GA
影响因子：
56.9
作者：
Kural, C;Kim, H;Selvin, PR
通讯作者：
Selvin, PR
影响因子：
7.8
作者：
Cavalli, V;Kujala, P;Goldstein, LSB
通讯作者：
Goldstein, LSB
影响因子：
16.2
作者：
Perlson, E;Hanz, S;Fainzilber, M
通讯作者：
Fainzilber, M
影响因子：
11.4
作者：
Görlich, D;Seewald, MJ;Ribbeck, K
通讯作者：
Ribbeck, K