title: Neurotrophin Promotes Neurite Outgrowth by Inhibiting Rif GTPase Activation Downstream of MAPKs and PI3K Signaling.
abstract: 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.
authors.affiliation: School of Life Sciences, Inner Mongolia University, Hohhot 010021, China. xiaoxiatian912@163.com.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Tian
authors.affiliation: School of Life Sciences, Inner Mongolia University, Hohhot 010021, China. huhehaoteyhj@163.com.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Yan
authors.affiliation: School of Life Sciences, Inner Mongolia University, Hohhot 010021, China. MandyLjy1996@163.com.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Life Sciences, Inner Mongolia University, Hohhot 010021, China. flieish0376@163.com.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wu
authors.affiliation: School of Life Sciences, Inner Mongolia University, Hohhot 010021, China. 13074782860@163.com.
authors.forename: Junyu
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Inner Mongolia University, Hohhot 010021, China. lifei.fan@imu.edu.cn.
authors.forename: Lifei
authors.initials: L
authors.lastname: Fan
mesh_terms: D000818:Animals; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008934:Mitogens / Q000494:pharmacology; D008954:Models, Biological; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000378:metabolism*; D016716:PC12 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D039961:Semaphorins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D003598:Cytoskeletal Proteins; D020558:GTP Phosphohydrolases; D020928:Mitogen-Activated Protein Kinases; D008934:Mitogens; D020932:Nerve Growth Factor; D009419:Nerve Tissue Proteins; D019869:Phosphatidylinositol 3-Kinases; D011956:Receptors, Cell Surface; D039961:Semaphorins; C575033:Plxna4 protein, rat; C504201:SEMA6A protein, human
keywords: Rif GTPase; neurite outgrowth; neurotrophin; semaphorin 6A