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Two PTP receptors mediate CSPG inhibition by convergent and divergent signaling pathways in neurons

https://hiroshima.repo.nii.ac.jp/records/2008794
https://hiroshima.repo.nii.ac.jp/records/2008794
a77960d9-3dfa-4749-80b8-998db8d34cdd
名前 / ファイル ライセンス アクション
SciRep_6_37152.pdf SciRep_6_37152.pdf (4.4 MB)
Item type デフォルトアイテムタイプ_(フル)(1)
公開日 2023-03-18
タイトル
タイトル Two PTP receptors mediate CSPG inhibition by convergent and divergent signaling pathways in neurons
言語 en
作成者 Otake, Yosuke

× Otake, Yosuke

en Otake, Yosuke

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Wong, Daniella

× Wong, Daniella

en Wong, Daniella

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Abdul-Muneer, P. M.

× Abdul-Muneer, P. M.

en Abdul-Muneer, P. M.

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Selzer, Michael E.

× Selzer, Michael E.

en Selzer, Michael E.

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Li, Shuxin

× Li, Shuxin

en Li, Shuxin

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アクセス権
アクセス権 open access
アクセス権URI http://purl.org/coar/access_right/c_abf2
権利情報
権利情報 © The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
内容記述
内容記述 Receptor protein tyrosine phosphatase σ (PTPσ) and its subfamily member LAR act as transmembrane receptors that mediate growth inhibition of chondroitin sulfate proteoglycans (CSPGs). Inhibition of either receptor increases axon growth into and beyond scar tissues after CNS injury. However, it is unclear why neurons express two similar CSPG receptors, nor whether they use the same or different intracellular pathways. We have now studied the signaling pathways of these two receptors using N2A cells and primary neurons derived from knockout mice. We demonstrate that both receptors share certain signaling pathways (RhoA, Akt and Erk), but also use distinct signals to mediate CSPG actions. Activation of PTPσ by CSPGs selectively inactivated CRMP2, APC, S6 kinase and CREB. By contrast LAR activation inactivated PKCζ, cofilin and LKB1. For the first time, we propose a model of the signaling pathways downstream of these two CSPG receptors. We also demonstrate that deleting both receptors exhibits additive enhancement of axon growth in adult neuronal cultures in vitro. Our findings elucidate the novel downstream pathways of CSPGs and suggest potential synergy of blocking their two PTP receptors.
言語 en
内容記述
内容記述タイプ Other
内容記述 This work was supported by research grants to SL from NIH (1R01NS079432, 1R21NS066114 and 1R01EY024575) and Shriners Research Foundation (SHC-86300-PHI and SHC-86200-PHI-16), and to MES from NIH (1R01NS092876) and Shriners Research Foundation (SHC-85400).
出版者
出版者 Nature Research
言語
言語 eng
資源タイプ
資源タイプ識別子 http://purl.org/coar/resource_type/c_6501
資源タイプ journal article
出版タイプ
出版タイプ VoR
出版タイプResource http://purl.org/coar/version/c_970fb48d4fbd8a85
関連情報
識別子タイプ DOI
関連識別子 10.1038/srep37152
関連情報
識別子タイプ PMID
関連識別子 27849007
関連情報
識別子タイプ DOI
関連識別子 https://doi.org/10.1038/srep37152
収録物識別子
収録物識別子タイプ ISSN
収録物識別子 2045-2322
開始ページ
開始ページ 37152
書誌情報 Scientific Reports
Scientific Reports

巻 6, p. 37152, 発行日 2016-11-16
旧ID 48646
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