Doublecortin-Like Kinases Promote Neuronal Survival and Induce Growth Cone Reformation via Distinct Mechanisms.
Doublecortin-Like Kinases Promote Neuronal Survival and Induce Growth Cone Reformation via Distinct Mechanisms.
复制标题
DOI：
10.1016/j.neuron.2015.10.005
复制
发表时间：
2015-11-18
期刊：
影响因子：
16.2
通讯作者：
He, Zhigang
中科院分区：
文献类型：
--
作者：
Nawabi, Homaira;Belin, Stephane;Cartoni, Romain;Williams, Philip R.;Wang, Chen;Latremoliere, Alban;Wang, Xuhua;Zhu, Junjie;Taub, Daniel G.;Fu, Xiaoqin;Yu, Bin;Gu, Xiaosong;Woolf, Clifford J.;Liu, Judy S.;Gabel, Christopher V.;Steen, Judith A.;He, Zhigang
轴突切断后，神经元存活和生长锥重建是轴突再生所必需的。我们发现，双皮质素样激酶（DCLKs），双皮质素（DCX）家族的成员在成人视网膜神经节细胞（RGC）中表达，通过不同的机制在这两个过程中发挥关键作用。过表达DCLK2可促进视神经损伤后轴突再生的起始和延长。这些影响取决于微管（MT）结合域和丝氨酸-脯氨酸丰富（S/P-丰富）地区的DCXs在同一分子中的顺式。虽然MT结合域是已知的MT结构稳定，我们表明，S/P丰富的区域防止F-肌动蛋白不稳定损伤轴突残端。此外，虽然DCXs与mTOR协同作用以刺激轴突再生，但单独它们可以通过调节损伤信号的逆行传播来促进神经元存活。因此，多功能DCX代表了促进受损神经元存活和再生的潜在靶点。
After axotomy, neuronal survival and growth cone re-formation are required for axon regeneration. We discovered that doublecortin-like kinases (DCLKs), members of the doublecortin (DCX) family expressed in the adult retinal ganglion cells (RGCs), play critical roles in both processes, through distinct mechanisms. Over-expression of DCLK2 accelerated growth cone re-formation in vitro and enhanced the initiation and elongation of axon re-growth after optic nerve injury. These effects depended on both the microtubule (MT)-binding domain and the serine-proline-rich (S/P-rich) region of DCXs in-cis in the same molecules. While the MT-binding domain is known to stabilize MT structures, we show that the S/P-rich region prevents F-actin destabilization in injured axon stumps. Additionally, while DCXs synergize with mTOR to stimulate axon regeneration, alone they can promote neuronal survival possibly through regulating the retrograde propagation of injury signals. Multifunctional DCXs thus represent potential targets for promoting both survival and regeneration of injured neurons.
登录
查看更多内容
影响因子：
64.5
作者：
Cho Y;Sloutsky R;Naegle KM;Cavalli V
通讯作者：
Cavalli V
影响因子：
3.5
作者：
Blackmore, Murray G.;Moore, Darcie L.;Smith, Robin P.;Goldberg, Jeffrey L.;Bixby, John L.;Lemmon, Vance P.
通讯作者：
Lemmon, Vance P.
DOI：
10.1523/jneurosci.4603-12.2013
发表时间：
2013-01-09
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Fu X;Brown KJ;Yap CC;Winckler B;Jaiswal JK;Liu JS
通讯作者：
Liu JS
影响因子：
5.3
作者：
Gumy, Laura F.;Chew, Daniel J.;Fawcett, James W.
通讯作者：
Fawcett, James W.
影响因子：
5.3
作者：
Friocourt, Gaelle;Liu, Judy S.;Parnavelas, John G.
通讯作者：
Parnavelas, John G.