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Hippocalcin Promotes Neuronal Differentiation and Inhibits Astrocytic Differentiation in Neural Stem Cells
Hippocalcin (HPCA) is a calcium-binding protein that is restricted to nervous tissue and contributes to neuronal activity. Here we report that, in addition to inducing neurogenesis, HPCA inhibits astrocytic differentiation of neural stem cells. It promotes neurogenesis by regulating protein kinase C...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5233403/ https://www.ncbi.nlm.nih.gov/pubmed/28017654 http://dx.doi.org/10.1016/j.stemcr.2016.11.009 |
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author | Park, Shin-Young Yoon, Sung Nyo Kang, Min-Jeong Lee, YunYoung Jung, Sung Jun Han, Joong-Soo |
author_facet | Park, Shin-Young Yoon, Sung Nyo Kang, Min-Jeong Lee, YunYoung Jung, Sung Jun Han, Joong-Soo |
author_sort | Park, Shin-Young |
collection | PubMed |
description | Hippocalcin (HPCA) is a calcium-binding protein that is restricted to nervous tissue and contributes to neuronal activity. Here we report that, in addition to inducing neurogenesis, HPCA inhibits astrocytic differentiation of neural stem cells. It promotes neurogenesis by regulating protein kinase Cα (PKCα) activation by translocating to the membrane and binding to phosphoinositide-dependent protein kinase 1 (PDK1), which induces PKCα phosphorylation. We also found that phospholipase D1 (PLD1) is implicated in the HPCA-mediated neurogenesis pathway; this enzyme promotes dephosphorylation of signal transducer and activator of transcription 3 (STAT3[Y705]), which is necessary for astrocytic differentiation. Moreover, we found that the SH2-domain-containing tyrosine phosphatase 1 (SHP-1) acts upstream of STAT3. Importantly, this SHP-1-dependent STAT3-inhibitory mechanism is closely involved in neurogenesis and suppression of gliogenesis by HPCA. Taken together, these observations suggest that HPCA promotes neuronal differentiation through activation of the PKCα/PLD1 cascade followed by activation of SHP-1, which dephosphorylates STAT3(Y705), leading to inhibition of astrocytic differentiation. |
format | Online Article Text |
id | pubmed-5233403 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-52334032017-01-23 Hippocalcin Promotes Neuronal Differentiation and Inhibits Astrocytic Differentiation in Neural Stem Cells Park, Shin-Young Yoon, Sung Nyo Kang, Min-Jeong Lee, YunYoung Jung, Sung Jun Han, Joong-Soo Stem Cell Reports Article Hippocalcin (HPCA) is a calcium-binding protein that is restricted to nervous tissue and contributes to neuronal activity. Here we report that, in addition to inducing neurogenesis, HPCA inhibits astrocytic differentiation of neural stem cells. It promotes neurogenesis by regulating protein kinase Cα (PKCα) activation by translocating to the membrane and binding to phosphoinositide-dependent protein kinase 1 (PDK1), which induces PKCα phosphorylation. We also found that phospholipase D1 (PLD1) is implicated in the HPCA-mediated neurogenesis pathway; this enzyme promotes dephosphorylation of signal transducer and activator of transcription 3 (STAT3[Y705]), which is necessary for astrocytic differentiation. Moreover, we found that the SH2-domain-containing tyrosine phosphatase 1 (SHP-1) acts upstream of STAT3. Importantly, this SHP-1-dependent STAT3-inhibitory mechanism is closely involved in neurogenesis and suppression of gliogenesis by HPCA. Taken together, these observations suggest that HPCA promotes neuronal differentiation through activation of the PKCα/PLD1 cascade followed by activation of SHP-1, which dephosphorylates STAT3(Y705), leading to inhibition of astrocytic differentiation. Elsevier 2016-12-22 /pmc/articles/PMC5233403/ /pubmed/28017654 http://dx.doi.org/10.1016/j.stemcr.2016.11.009 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Park, Shin-Young Yoon, Sung Nyo Kang, Min-Jeong Lee, YunYoung Jung, Sung Jun Han, Joong-Soo Hippocalcin Promotes Neuronal Differentiation and Inhibits Astrocytic Differentiation in Neural Stem Cells |
title | Hippocalcin Promotes Neuronal Differentiation and Inhibits Astrocytic Differentiation in Neural Stem Cells |
title_full | Hippocalcin Promotes Neuronal Differentiation and Inhibits Astrocytic Differentiation in Neural Stem Cells |
title_fullStr | Hippocalcin Promotes Neuronal Differentiation and Inhibits Astrocytic Differentiation in Neural Stem Cells |
title_full_unstemmed | Hippocalcin Promotes Neuronal Differentiation and Inhibits Astrocytic Differentiation in Neural Stem Cells |
title_short | Hippocalcin Promotes Neuronal Differentiation and Inhibits Astrocytic Differentiation in Neural Stem Cells |
title_sort | hippocalcin promotes neuronal differentiation and inhibits astrocytic differentiation in neural stem cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5233403/ https://www.ncbi.nlm.nih.gov/pubmed/28017654 http://dx.doi.org/10.1016/j.stemcr.2016.11.009 |
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