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Int. J. Mol. Sci. 2017, 18(1), 148;

Neurotrophin Promotes Neurite Outgrowth by Inhibiting Rif GTPase Activation Downstream of MAPKs and PI3K Signaling

School of Life Sciences, Inner Mongolia University, Hohhot 010021, China
Author to whom correspondence should be addressed.
Academic Editor: Cesar Borlongan
Received: 3 November 2016 / Revised: 1 January 2017 / Accepted: 6 January 2017 / Published: 13 January 2017
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Full-Text   |   PDF [2679 KB, uploaded 13 January 2017]   |  


Members of the well-known semaphorin family of proteins can induce both repulsive and attractive signaling in neural network formation and their cytoskeletal effects are mediated in part by small guanosine 5’-triphosphatase (GTPases). The aim of this study was to investigate the cellular role of Rif GTPase in the neurotrophin-induced neurite outgrowth. By using PC12 cells which are known to cease dividing and begin to show neurite outgrowth responding to nerve growth factor (NGF), we found that semaphorin 6A was as effective as nerve growth factor at stimulating neurite outgrowth in PC12 cells, and that its neurotrophic effect was transmitted through signaling by mitogen-activated protein kinases (MAPKs) and phosphatidylinositol-3-kinase (PI3K). We further found that neurotrophin-induced neurite formation in PC12 cells could be partially mediated by inhibition of Rif GTPase activity downstream of MAPKs and PI3K signaling. In conclusion, we newly identified Rif as a regulator of the cytoskeletal rearrangement mediated by semaphorins. View Full-Text
Keywords: semaphorin 6A; neurotrophin; neurite outgrowth; Rif GTPase semaphorin 6A; neurotrophin; neurite outgrowth; Rif GTPase

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Tian, X.; Yan, H.; Li, J.; Wu, S.; Wang, J.; Fan, L. Neurotrophin Promotes Neurite Outgrowth by Inhibiting Rif GTPase Activation Downstream of MAPKs and PI3K Signaling. Int. J. Mol. Sci. 2017, 18, 148.

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