Stuttgart Research Center Systems Biology, University of Stuttgart, Stuttgart, Germany.
Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, Germany.
Elife. 2018 Jul 20;7:e35907. doi: 10.7554/eLife.35907.
Protein kinase D (PKD) is a family of serine/threonine kinases that is required for the structural integrity and function of the Golgi complex. Despite its importance in the regulation of Golgi function, the molecular mechanisms regulating PKD activity are still incompletely understood. Using the genetically encoded PKD activity reporter G-PKDrep we now uncover a Rho signaling network comprising GEF-H1, the RhoGAP DLC3, and the Rho effector PLCε that regulate the activation of PKD at trans-Golgi membranes. We further show that this molecular network coordinates the formation of TGN-derived Rab6-positive transport carriers delivering cargo for localized exocytosis at focal adhesions.
蛋白激酶 D(PKD)是丝氨酸/苏氨酸激酶家族的一员,对于高尔基体复合物的结构完整性和功能至关重要。尽管它在高尔基体功能的调节中具有重要作用,但调节 PKD 活性的分子机制仍不完全清楚。使用基因编码的 PKD 活性报告基因 G-PKDrep,我们现在揭示了一个 Rho 信号网络,该网络由 GEF-H1、RhoGAP DLC3 和 Rho 效应物 PLCε 组成,调节 PKD 在反式高尔基体膜上的激活。我们进一步表明,这个分子网络协调了 TGN 衍生的 Rab6 阳性运输载体的形成,这些载体为局部胞吐作用运送货物到粘着斑。