c-Jun in Schwann cells promotes axonal regeneration and motoneuron survival via paracrine signaling.
c-Jun in Schwann cells promotes axonal regeneration and motoneuron survival via paracrine signaling.
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DOI：
10.1083/jcb.201205025
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发表时间：
2012-07-09
期刊：
影响因子：
--
通讯作者：
Behrens A
中科院分区：
文献类型：
--
作者：
Fontana X;Hristova M;Da Costa C;Patodia S;Thei L;Makwana M;Spencer-Dene B;Latouche M;Mirsky R;Jessen KR;Klein R;Raivich G;Behrens A
雪旺细胞中的c-Jun促进Ret配体GDNF和Artemin的表达，这导致损伤后运动神经元存活和轴突再生增强。AP-1转录因子c-Jun是神经元轴突反应的主要调节因子。c-Jun还作为雪旺细胞（SC）中髓鞘形成的负调节剂起作用，并且在轴突损伤时在SC中被强烈地再激活。我们在这里证明，损伤后，c-Jun的情况下，特别是在SC造成受损的轴突再生和严重增加神经元细胞死亡。c-Jun缺陷导致几种神经营养因子的表达降低，并且GDNF和Artemin（两者都编码Ret受体酪氨酸激酶的配体）被鉴定为新的直接c-Jun靶基因。Ret基因失活，特别是在神经元中导致再生缺陷，而不影响运动神经元的存活，相反，重组GDNF和Artemin蛋白的管理大大改善受损的c-Jun缺陷引起的再生。这些结果揭示了c-Jun在SC中响应于轴突损伤的意外功能，并鉴定了旁分泌Ret信号传导作为再生期间SC中c-Jun功能的重要介质。
c-Jun in Schwann cells promotes the expression of Ret ligands GDNF and Artemin, which leads to enhanced motoneuron survival and axonal regeneration after injury. The AP-1 transcription factor c-Jun is a master regulator of the axonal response in neurons. c-Jun also functions as a negative regulator of myelination in Schwann cells (SCs) and is strongly reactivated in SCs upon axonal injury. We demonstrate here that, after injury, the absence of c-Jun specifically in SCs caused impaired axonal regeneration and severely increased neuronal cell death. c-Jun deficiency resulted in decreased expression of several neurotrophic factors, and GDNF and Artemin, both of which encode ligands for the Ret receptor tyrosine kinase, were identified as novel direct c-Jun target genes. Genetic inactivation of Ret specifically in neurons resulted in regeneration defects without affecting motoneuron survival and, conversely, administration of recombinant GDNF and Artemin protein substantially ameliorated impaired regeneration caused by c-Jun deficiency. These results reveal an unexpected function for c-Jun in SCs in response to axonal injury, and identify paracrine Ret signaling as an important mediator of c-Jun function in SCs during regeneration.
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影响因子：
64.5
作者：
Bonanomi D;Chivatakarn O;Bai G;Abdesselem H;Lettieri K;Marquardt T;Pierchala BA;Pfaff SL
通讯作者：
Pfaff SL
影响因子：
11.4
作者：
Behrens, A;Sibilia, M;Wagner, EF
通讯作者：
Wagner, EF
影响因子：
7.8
作者：
Heumann, R;Goemans, C;Bartsch, D;Lingenhohl, K;Waldmeier, P C;Hengerer, B;Allegrini, P R;Schellander, K;Wagner, E F;Arendt, T;Kamdem, R H;Obst-Pernberg, K;Narz, F;Wahle, P;Berns, H
通讯作者：
Berns, H
影响因子：
--
作者：
ABERCROMBIE, M
通讯作者：
ABERCROMBIE, M
非神经元细胞中神经生长因子合成的变化响应坐骨神经横向。
影响因子：
7.8
作者：
Heumann, R;Korsching, S;Bandtlow, C;Thoenen, H
通讯作者：
Thoenen, H