翻译：转录因子分泌端促进轴突生长。
Promotion of Axon Growth by the Secreted End of a Transcription Factor.
机构信息
Integrated Program in Cellular, Molecular and Biomedical Studies, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
出版信息
Cell Rep. 2019 Oct 8;29(2):363-377.e5. doi: 10.1016/j.celrep.2019.08.101.
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. S2P and CREB3L2 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.
轴突的生长受到环境中产生的吸引和排斥线索的外部调节。此外，内在途径也控制着轴突的发育，尽管轴突本身影响其生长的程度尚不清楚。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，并将其鉴定为 ER 应激诱导转录因子 CREB3L2 的 C 端，它是由感觉神经元中的位点 2 蛋白酶（S2P）切割产生的。S2P 和 CREB3L2 的敲低或轴突 S2P 的抑制会干扰轴突的生长，而 C 端 CREB3L2 足以挽救这些效应。C 端 CREB3L2 与 Shh 形成复合物，并稳定其与发育中的轴突上的 Patched-1 受体的结合。我们的结果揭示了 S2P 下游促进轴突生长的神经元内在途径。
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