Department of Anatomy and Neurobiology, Washington University in St Louis, School of Medicine, MO 63110-1093, USA.
EMBO J. 2012 Jun 12;31(14):3063-78. doi: 10.1038/emboj.2012.160.
Axon regeneration is an essential process to rebuild functional connections between injured neurons and their targets. Regenerative axonal growth requires alterations in axonal microtubule dynamics, but the signalling mechanisms involved remain incompletely understood. Our results reveal that axon injury induces a gradient of tubulin deacetylation, which is required for axon regeneration both in vitro and in vivo. This injury-induced tubulin deacetylation is specific to peripheral neurons and fails to occur in central neurons. We found that tubulin deacetylation is initiated by calcium influx at the site of injury, and requires protein kinase C-mediated activation of the histone deacetylase 5 (HDAC5). Our findings identify HDAC5 as a novel injury-regulated tubulin deacetylase that plays an essential role in growth cone dynamics and axon regeneration. In addition, our results suggest a mechanism for the spatial control of tubulin modifications that is required for axon regeneration.
轴突再生是重建受损神经元与其靶标之间功能性连接的重要过程。再生轴突生长需要改变轴突微管动力学，但涉及的信号机制仍不完全清楚。我们的结果表明，轴突损伤诱导微管去乙酰化的梯度，这对于体外和体内的轴突再生都是必需的。这种损伤诱导的微管去乙酰化是周围神经元特有的，而中枢神经元则不会发生。我们发现，微管去乙酰化是由损伤部位的钙内流引发的，需要蛋白激酶 C 介导的组蛋白去乙酰化酶 5（HDAC5）的激活。我们的发现确定了 HDAC5 是一种新的损伤调节的微管去乙酰化酶，它在生长锥动力学和轴突再生中发挥着重要作用。此外，我们的结果还为轴突再生所需的微管修饰的空间控制提供了一种机制。
