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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4682924/ https://www.ncbi.nlm.nih.gov/pubmed/26670864 http://dx.doi.org/10.1371/journal.pone.0144948 |
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author | Ding, Yuemin Li, Yuying Lu, Lingchao Zhang, Ruyi Zeng, Linghui Wang, Linlin Zhang, Xiong |
author_facet | Ding, Yuemin Li, Yuying Lu, Lingchao Zhang, Ruyi Zeng, Linghui Wang, Linlin Zhang, Xiong |
author_sort | Ding, Yuemin |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-4682924 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-46829242015-12-31 Inhibition of Nischarin Expression Promotes Neurite Outgrowth through Regulation of PAK Activity Ding, Yuemin Li, Yuying Lu, Lingchao Zhang, Ruyi Zeng, Linghui Wang, Linlin Zhang, Xiong PLoS One Research Article 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. Public Library of Science 2015-12-15 /pmc/articles/PMC4682924/ /pubmed/26670864 http://dx.doi.org/10.1371/journal.pone.0144948 Text en © 2015 Ding et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Ding, Yuemin Li, Yuying Lu, Lingchao Zhang, Ruyi Zeng, Linghui Wang, Linlin Zhang, Xiong Inhibition of Nischarin Expression Promotes Neurite Outgrowth through Regulation of PAK Activity |
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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4682924/ https://www.ncbi.nlm.nih.gov/pubmed/26670864 http://dx.doi.org/10.1371/journal.pone.0144948 |
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