Spatio-temporal regulation of cellular trafficking and signal transduction

(1)神经元是两极细胞，在轴突和树突中含有不同的蛋白质组。突触囊泡和许多突触蛋白仅定位于突触前区域，而不定位于树突。我们发现，MAPKKK样激酶LRK-1的作用途径与UNC-16相同，是形成适当体积的高尔基体运输小泡所必需的。(2)表皮生长因子受体(EGFR)的激活触发了转运事件，将受体从细胞表面重新定位到细胞内的间隔室。这些事件对于有丝分裂的EGFR信号的调节是重要的。我们发现富含亮氨酸的重复蛋白激酶1(LRRK1)是Roco激酶家族的成员，通过与Grb2相互作用，与激活的EGFR形成复合体，参与EGFR从早期到晚期的转运。我们发现，EGFR通过Tyr-944的磷酸化负性调节LRRK1的激酶活性，这是EGFR正确的内体转运所必需的。

(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.