Promotion of Axon Growth by the Secreted End of a Transcription Factor
Promotion of Axon Growth by the Secreted End of a Transcription Factor
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DOI：
10.1016/j.celrep.2019.08.101
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发表时间：
2019-10-08
期刊：
影响因子：
8.8
通讯作者：
Hengst, Ulrich
中科院分区：
文献类型：
--
作者：
McCurdy, Ethan P.;Chung, Kyung Min;Hengst, Ulrich
轴突的生长受环境中产生的吸引和排斥的线索的外部调节。此外，尽管轴突本身能在多大程度上影响自身的生长，但轴突发育的内在途径是未知的。我们发现背根神经节(DRG)轴突分泌一种支持轴突生长的因子，并确定它是内质网应激诱导的转录因子CREB3L2的C末端，该因子是由感觉神经元中的S2P酶(S2P)裂解产生的。S2P2和CREB3L2基因敲除或抑制轴突S2P干扰轴突的生长，C端CREB3L2足以挽救这些影响。C-末端CREB3L2与Shh形成复合体，并稳定其与发育中轴突上的Patched-1受体的联系。我们的结果揭示了S2P下游的一条促进轴突生长的神经元内部通路。
Axon growth is regulated externally by attractive and repulsive cues generated in the environment. In addition, intrinsic pathways govern axon development, although the extent to which axons themselves can influence their own growth is unknown. We find that dorsal root ganglion (DRG) axons secrete a factor supporting axon growth and identify it as the C terminus of the ER stress-induced transcription factor CREB3L2, which is generated by site 2 protease (S2P) cleavage in sensory neurons. S2PandCREB3L2 knockdown or inhibition of axonal S2P interfere with the growth of axons, and C-terminal CREB3L2 is sufficient to rescue these effects. C-terminal CREB3L2 forms a complex with Shh and stabilizes its association with the Patched-1 receptor on developing axons. Our results reveal a neuron-intrinsic pathway downstream of S2P that promotes axon growth.