Inhibition of Nischarin Expression Promotes Neurite Outgrowth through Regulation of PAK Activity.

Nischarin is a cytoplasmic protein expressed in various organs that plays an inhibitory role in cell migration and invasion and the carcinogenesis of breast cancer cells. We previously reported that Nischarin is highly expressed in neuronal cell lines and is differentially expressed in the brain tis...

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Main Authors: Yuemin Ding, Yuying Li, Lingchao Lu, Ruyi Zhang, Linghui Zeng, Linlin Wang, Xiong Zhang
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0144948
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author Yuemin Ding
Yuying Li
Lingchao Lu
Ruyi Zhang
Linghui Zeng
Linlin Wang
Xiong Zhang
author_facet Yuemin Ding
Yuying Li
Lingchao Lu
Ruyi Zhang
Linghui Zeng
Linlin Wang
Xiong Zhang
author_sort Yuemin Ding
collection DOAJ
description Nischarin is a cytoplasmic protein expressed in various organs that plays an inhibitory role in cell migration and invasion and the carcinogenesis of breast cancer cells. We previously reported that Nischarin is highly expressed in neuronal cell lines and is differentially expressed in the brain tissue of adult rats. However, the physiological function of Nischarin in neural cells remains unknown. Here, we show that Nischarin is expressed in rat primary cortical neurons but not in astrocytes. Nischarin is localized around the nucleus and dendrites. Using shRNA to knockdown the expression of endogenous Nischarin significantly increases the percentage of neurite-bearing cells, remarkably increases neurite length, and accelerates neurite extension in neuronal cells. Silencing Nischarin expression also promotes dendrite elongation in rat cortical neurons where Nischarin interacts with p21-activated kinase 1/2 (PAK1/2) and negatively regulates phosphorylation of both PAK1 and PAK2. The stimulation of neurite growth observed in cells with decreased levels of Nischarin is partially abolished by IPA3-mediated inhibition of PAK1 activity. Our findings indicate that endogenous Nischarin inhibits neurite outgrowth by blocking PAK1 activation in neurons.
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spelling doaj.art-cb235f251fd949999abf45ef53d493a52022-12-21T19:15:39ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011012e014494810.1371/journal.pone.0144948Inhibition of Nischarin Expression Promotes Neurite Outgrowth through Regulation of PAK Activity.Yuemin DingYuying LiLingchao LuRuyi ZhangLinghui ZengLinlin WangXiong ZhangNischarin is a cytoplasmic protein expressed in various organs that plays an inhibitory role in cell migration and invasion and the carcinogenesis of breast cancer cells. We previously reported that Nischarin is highly expressed in neuronal cell lines and is differentially expressed in the brain tissue of adult rats. However, the physiological function of Nischarin in neural cells remains unknown. Here, we show that Nischarin is expressed in rat primary cortical neurons but not in astrocytes. Nischarin is localized around the nucleus and dendrites. Using shRNA to knockdown the expression of endogenous Nischarin significantly increases the percentage of neurite-bearing cells, remarkably increases neurite length, and accelerates neurite extension in neuronal cells. Silencing Nischarin expression also promotes dendrite elongation in rat cortical neurons where Nischarin interacts with p21-activated kinase 1/2 (PAK1/2) and negatively regulates phosphorylation of both PAK1 and PAK2. The stimulation of neurite growth observed in cells with decreased levels of Nischarin is partially abolished by IPA3-mediated inhibition of PAK1 activity. Our findings indicate that endogenous Nischarin inhibits neurite outgrowth by blocking PAK1 activation in neurons.https://doi.org/10.1371/journal.pone.0144948
spellingShingle Yuemin Ding
Yuying Li
Lingchao Lu
Ruyi Zhang
Linghui Zeng
Linlin Wang
Xiong Zhang
Inhibition of Nischarin Expression Promotes Neurite Outgrowth through Regulation of PAK Activity.
PLoS ONE
title Inhibition of Nischarin Expression Promotes Neurite Outgrowth through Regulation of PAK Activity.
title_full Inhibition of Nischarin Expression Promotes Neurite Outgrowth through Regulation of PAK Activity.
title_fullStr Inhibition of Nischarin Expression Promotes Neurite Outgrowth through Regulation of PAK Activity.
title_full_unstemmed Inhibition of Nischarin Expression Promotes Neurite Outgrowth through Regulation of PAK Activity.
title_short Inhibition of Nischarin Expression Promotes Neurite Outgrowth through Regulation of PAK Activity.
title_sort inhibition of nischarin expression promotes neurite outgrowth through regulation of pak activity
url https://doi.org/10.1371/journal.pone.0144948
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