Meli Rajeshwari, Weisová Petronela, Propst Friedrich
Department of Biochemistry and Cell Biology, Max F. Perutz Laboratories (MFPL), University of Vienna, Vienna Biocenter (VBC), 1030, Vienna, Austria.
PLoS One. 2015 Mar 16;10(3):e0119524. doi: 10.1371/journal.pone.0119524. eCollection 2015.
Draxin is an important axon guidance cue necessary for the formation of forebrain commissures including the corpus callosum, but the molecular details of draxin signaling are unknown. To unravel how draxin signals are propagated we used murine cortical neurons and genetic and pharmacological approaches. We found that draxin-induced growth cone collapse critically depends on draxin receptors (deleted in colorectal cancer, DCC), inhibition of protein kinase B/Akt, activation of GSK-3β (glycogen synthase kinase-3β) and the presence of microtubule-associated protein MAP1B. This study, for the first time elucidates molecular events in draxin repulsion, links draxin and DCC to MAP1B and identifies a novel MAP1B-depenent GSK-3β pathway essential for chemo-repulsive axon guidance cue signaling.
Draxin是前脑连合（包括胼胝体）形成所必需的一种重要轴突导向信号，但Draxin信号传导的分子细节尚不清楚。为了阐明Draxin信号是如何传播的，我们使用了小鼠皮层神经元以及遗传学和药理学方法。我们发现，Draxin诱导的生长锥塌陷关键取决于Draxin受体（结直肠癌缺失基因，DCC）、蛋白激酶B/Akt的抑制、糖原合酶激酶-3β（GSK-3β）的激活以及微管相关蛋白MAP1B的存在。本研究首次阐明了Draxin排斥作用中的分子事件，将Draxin和DCC与MAP1B联系起来，并确定了一种新的依赖于MAP1B的GSK-3β途径，该途径对于化学排斥性轴突导向信号传导至关重要。
