Kabayama Hiroyuki, Tokushige Naoko, Takeuchi Makoto, Mikoshiba Katsuhiko
Laboratory for Developmental Neurobiology, Brain Science Institute, Institute of Physical and Chemical Research RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Neurosci Lett. 2008 May 16;436(3):340-4. doi: 10.1016/j.neulet.2008.03.061. Epub 2008 Mar 26.
Neurite outgrowth is crucial for neural circuit formation. Intracellular membrane trafficking is involved in the cell surface expansion that is necessary for neurite outgrowth. It is known that syntaxin 6 is predominantly located in the Golgi region in undifferentiated PC12 cells and that it regulates trans-Golgi network trafficking and the secretory pathway via its coiled-coil domains. However, whether it also regulates neurite outgrowth remains unknown. In this paper, we found that syntaxin 6 was located both in the Golgi apparatus and the distal tips of the neurites of nerve growth factor (NGF)-treated PC12 cells. We also showed that the overexpression of the first coiled-coil domain of syntaxin 6 inhibited NGF-dependent neurite outgrowth. However, the coiled-coil domain-disrupting mutant had little effect on neurite outgrowth. These results suggest that the first coiled-coil domain of syntaxin 6 plays a crucial role in NGF-dependent neurite outgrowth.
神经突生长对于神经回路的形成至关重要。细胞内膜运输参与神经突生长所必需的细胞表面扩张。已知 syntaxin 6 在未分化的 PC12 细胞中主要位于高尔基体区域,并且它通过其卷曲螺旋结构域调节反式高尔基体网络运输和分泌途径。然而,它是否也调节神经突生长仍不清楚。在本文中,我们发现 syntaxin 6 位于神经生长因子(NGF)处理的 PC12 细胞的高尔基体和神经突的远端尖端。我们还表明,syntaxin 6 的第一个卷曲螺旋结构域的过表达抑制了 NGF 依赖性神经突生长。然而,卷曲螺旋结构域破坏突变体对神经突生长几乎没有影响。这些结果表明,syntaxin 6 的第一个卷曲螺旋结构域在 NGF 依赖性神经突生长中起关键作用。