Kobayashi Takahiko, Nagase Fumiaki, Hotta Kohji, Oka Kotaro
Center for Biosciences and Informatics, School of Fundamental Sciences and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa, Japan.
Sci Rep. 2013 Nov 1;3:3118. doi: 10.1038/srep03118.
Axon guidance involves multiple second messenger signal transduction pathways. Although each signal transduction pathway has been characterized, only a few studies have examined crosstalk between these cascades. Here, we applied a simultaneous second messenger imaging method to the growth cone and demonstrated correlations between cAMP, cGMP, and Ca(2+). The levels of cAMP and cGMP in non-stimulated freely extending growth cones showed a negative correlation without delay. Although there was no direct correlation between cAMP and Ca(2+), examination of cross correlations using small time windows showed frequent switching behavior from negative to positive and vice versa. Furthermore, spatially asymmetric cAMP and cGMP signals in freely deviating growth cones were visualized directly. These results indicate that we succeed in relating second messenger crosstalk to growth cone deviation and extension, and also indicate the possibility of predicting axon guidance from this second messenger crosstalk.
轴突导向涉及多个第二信使信号转导途径。尽管每个信号转导途径都已得到表征，但只有少数研究考察了这些级联反应之间的相互作用。在这里，我们将一种同时进行第二信使成像的方法应用于生长锥，并证明了环磷酸腺苷（cAMP）、环磷酸鸟苷（cGMP）和钙离子（Ca²⁺）之间的相关性。在未受刺激的自由延伸生长锥中，cAMP和cGMP的水平呈现出无延迟的负相关。虽然cAMP和Ca²⁺之间没有直接相关性，但使用小时间窗口检查交叉相关性时发现，其频繁出现从负到正以及反之亦然的转换行为。此外，还直接观察到了自由偏离的生长锥中空间不对称的cAMP和cGMP信号。这些结果表明，我们成功地将第二信使的相互作用与生长锥的偏离和延伸联系起来，也表明了从这种第二信使相互作用预测轴突导向的可能性。
