Spatio-temporal regulation of cellular trafficking and signal transduction

(1)神经元是极化细胞，在其轴突和树突中含有不同的蛋白质组。突触囊泡（SV）和许多SV蛋白只定位于突触前区域，而不是树突。我们发现，MAPKKK样激酶LRK-1的行为在相同的途径，作为ESTA-16和所需的适当体积的运输囊泡从高尔基体的形成。(2)表皮生长因子受体（EGFR）的激活触发将受体从细胞表面重新定位到细胞内吞区室的运输事件。这些事件对于调节促有丝分裂EGFR信号传导是重要的。我们发现，富含亮氨酸的重复序列激酶1（LRRK 1），ROCO激酶家族的成员，通过与Grb 2的相互作用与活化的EGFR形成复合物，并参与EGFR从早期到晚期内体的运输。我们发现EGFR通过Tyr-944磷酸化负调节LRRK 1的激酶活性，这是EGFR适当内体运输所必需的。

(1) Neurons are polarized cells that contain distinct sets of proteins in their axons and dendrites. Synaptic vesicles(SV) and many SV proteins are exclusively localized in the presynaptic regions but not in dendrites. We found that a MAPKKK-like kinase LRK-1 acts in the same pathway as UNC-16 and is required for the formation of proper volume of transport vesicles from Golgi apparatus.(2) Activation of the epidermal growth factor receptor(EGFR) triggers trafficking events that relocalize receptors from the cell surface to intracellular endocytic compartments. These events are important for the regulation of mitogenic EGFR signaling. We revealed that leucine-rich repeat kinase 1(LRRK1), a member of ROCO kinase family, forms a complex with activated EGFR through an interaction with Grb2 and is involved in the trafficking of EGFR from early to late endosomes. We showed that EGFR negatively regulates the kinase activity of LRRK1 by Tyr-944 phosphorylation and that this is required for proper endosomal trafficking of EGFR.