Xie Yi, Hong Yan, Ma Xiao-Yue, Ren Xiu-Rong, Ackerman Susan, Mei Lin, Xiong Wen-Cheng
Institute of Molecular Medicine & Genomics and Department of Neurology, Medical College of Georgia, Augusta, Georgia 30809, USA.
J Biol Chem. 2006 Feb 3;281(5):2605-11. doi: 10.1074/jbc.M512767200. Epub 2005 Nov 30.
Netrins, a family of secreted molecules, play important roles in axon pathfinding during nervous system development. Although phosphatidylinositol signaling has been implicated in this event, how netrin-1 regulates phosphatidylinositol signaling remains poorly understood. Here we provide evidence that netrin-1 stimulates phosphatidylinositol bisphosphate hydrolysis in cortical neurons. This event appears to be mediated by DCC (deleted in colorectal cancer), but not neogenin or Unc5h2. Netrin-1 induces phospholipase Cgamma (PLCgamma) tyrosine phosphorylation. Inhibition of PLC activity attenuates netrin-1-induced cortical neurite outgrowth. These results suggest that netrin-1 regulates phosphatidylinositol turnover and demonstrate a crucial role of PLC signaling in netrin-1-induced neurite elongation.
Netrins是一类分泌分子家族，在神经系统发育过程中的轴突导向中发挥重要作用。尽管磷脂酰肌醇信号传导与这一过程有关，但netrin-1如何调节磷脂酰肌醇信号传导仍知之甚少。在此，我们提供证据表明netrin-1刺激皮层神经元中的磷脂酰肌醇二磷酸水解。这一事件似乎由结直肠癌缺失基因（DCC）介导，而非新基因或Unc5h2。Netrin-1诱导磷脂酶Cγ（PLCγ）酪氨酸磷酸化。抑制PLC活性会减弱netrin-1诱导的皮层神经突生长。这些结果表明netrin-1调节磷脂酰肌醇周转，并证明PLC信号传导在netrin-1诱导的神经突伸长中起关键作用。
