Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) Regulates Neurite Outgrowth Through the Activation of Akt/mTOR and Erk/mTOR Signaling Pathways

Wen Wen; Yongchao Wang; Hui Li; Hong Xu; Mei Xu; Jacqueline A Frank; Murong Ma; Jia Luo

doi:10.3389/fnmol.2020.560020

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Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) Regulates Neurite Outgrowth Through the Activation of Akt/mTOR and Erk/mTOR Signaling Pathways

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Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) Regulates Neurite Outgrowth Through the Activation of Akt/mTOR and Erk/mTOR Signaling Pathways

Wen Wen, Yongchao Wang, Hui Li, Hong Xu, Mei Xu, Jacqueline A Frank, Murong Ma and Jia Luo

Frontiers in molecular neuroscience, Vol.13, pp.560020-560020

09/24/2020

DOI: 10.3389/fnmol.2020.560020

PMCID: PMC7541815

PMID: 33071755

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https://doi.org/10.3389/fnmol.2020.560020View

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Abstract

Neurite outgrowth is essential for brain development and the recovery of brain injury and neurodegenerative diseases. In this study, we examined the role of the neurotrophic factor MANF in regulating neurite outgrowth. We generated MANF knockout (KO) neuro2a (N2a) cell lines using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 and demonstrated that MANF KO N2a cells failed to grow neurites in response to RA stimulation. Using MANF siRNA, this finding was confirmed in human SH-SY5Y neuronal cell line. Nevertheless, MANF overexpression by adenovirus transduction or addition of MANF into culture media facilitated the growth of longer neurites in RA-treated N2a cells. MANF deficiency resulted in inhibition of Akt, Erk, mTOR, and P70S6, and impaired protein synthesis. MANF overexpression on the other hand facilitated the growth of longer neurites by activating Akt, Erk, mTOR, and P70S6. Pharmacological blockade of Akt, Erk or mTOR eliminated the promoting effect of MANF on neurite outgrowth. These findings suggest that MANF positively regulated neurite outgrowth by activating Akt/mTOR and Erk/mTOR signaling pathways.

Akt

Erk

MANF

mTOR

neurite outgrowth

neuronal differentiation

Neuroscience

neurotrophic factor

protein synthesis

Details

Title: Subtitle: Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) Regulates Neurite Outgrowth Through the Activation of Akt/mTOR and Erk/mTOR Signaling Pathways
Creators: Wen Wen - University of Iowa
Yongchao Wang - University of Kentucky
Hui Li - University of Iowa
Hong Xu - University of Kentucky
Mei Xu - University of Kentucky
Jacqueline A Frank - University of Kentucky
Murong Ma - University of Kentucky
Jia Luo - University of Iowa
Resource Type: Journal article
Publication Details: Frontiers in molecular neuroscience, Vol.13, pp.560020-560020
DOI: 10.3389/fnmol.2020.560020
PMID: 33071755
PMCID: PMC7541815
NLM abbreviation: Front Mol Neurosci
ISSN: 1662-5099
eISSN: 1662-5099
Publisher: Frontiers Media S.A
Grant note: AA017226; AA015407 / National Institute on Alcohol Abuse and Alcoholism
Language: English
Date published: 09/24/2020
Academic Unit: Pathology
Record Identifier: 9984186410902771

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