Authors: Kanghyun Ryoo Sanggil Hwang Kwang Je Kim EuiJu Choi
Publish Date: 2014/12/30
Volume: 402, Issue: 1-2, Pages: 33-40
Abstract
RC3/neurogranin is a postsynaptic protein and plays pivotal roles in spatial learning and emotional anxiety as well as synaptic plasticity The expression level of RC3 is dynamically changed during developmental stages but the function of RC3 in brain development is not well understood yet Neurotrophins interact with tropomyosinrelated kinase receptors to activate Ras–extracellular signalregulated kinase ERK pathway and can also induce neuronal differentiation In this study we demonstrate that RC3 inhibits Ras–ERK pathway by interaction with Ras and controls neurite outgrowth induced by neurotrophins In PC12 cells RC3 inhibits nerve growth factor NGFinduced activation of Ras and thereby ERK1/2 signaling cascade as well as neurite outgrowth induced by NGF We found Ras is the target of the inhibitory function of RC3 because RC3 interacts with Ras and suppresses the elevated affinity of Ras to Rasbinding domain of Raf1 Meanwhile already activated Raf1 by Ras activity is not affected by RC3 Furthermore depletion of RC3 by RNA interference drastically enhances the stimulation of ERK1/2 and neurite outgrowth induced by brainderived neurotrophic factor in hippocampal neurons These findings suggest that RC3 is a novel natural inhibitor of RasERK1/2 signaling axis leading to negatively regulate neuronal differentiation induced by neurotrophinsWe thank Drs R Krug University of Wuerzburg Germany for Raf1 and MEK1K97R cDNA and C Herrmann Max Plank Institute of Molecular Physiology Germany for GSTRafRBD cDNA This work was supported by a National Research Foundation Grant 20060093855 and a NRF Grant 20110030141 through the National Research Foundation of Korea funded by the Ministry of Science ICT Future Planning MEST of the Korea and by a Korea University Grant EJC
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