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Int J Mol Sci. 2017 Jan 13;18(1). pii: E148. doi: 10.3390/ijms18010148.

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

Author information

1
School of Life Sciences, Inner Mongolia University, Hohhot 010021, China. xiaoxiatian912@163.com.
2
School of Life Sciences, Inner Mongolia University, Hohhot 010021, China. huhehaoteyhj@163.com.
3
School of Life Sciences, Inner Mongolia University, Hohhot 010021, China. MandyLjy1996@163.com.
4
School of Life Sciences, Inner Mongolia University, Hohhot 010021, China. flieish0376@163.com.
5
School of Life Sciences, Inner Mongolia University, Hohhot 010021, China. 13074782860@163.com.
6
School of Life Sciences, Inner Mongolia University, Hohhot 010021, China. lifei.fan@imu.edu.cn.

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.

KEYWORDS:

Rif GTPase; neurite outgrowth; neurotrophin; semaphorin 6A

PMID:
28098758
PMCID:
PMC5297781
DOI:
10.3390/ijms18010148
[Indexed for MEDLINE]
Free PMC Article

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