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α1,6‐Fucosylation regulates neurite formation via the activin/phospho‐Smad2 pathway in PC12 cells: the implicated dual effects of Fut8 for TGF‐β/activin‐mediated signaling

2013; Wiley; Volume: 27; Issue: 10 Linguagem: Inglês

10.1096/fj.12-225805

1530-6860

Wei Gu, Tomohiko Fukuda, Tomoya Isaji, H Hashimoto, Yuqin Wang, Jianguo Gu,

TGF-β signaling in diseases

The FASEB JournalVolume 27, Issue 10 p. 3947-3958 Research CommunicationFree to Read α1,6-Fucosylation regulates neurite formation via the activin/phospho-Smad2 pathway in PC12 cells: the implicated dual effects of Fut8 for TGF-β/activin-mediated signaling Wei Gu, Wei Gu Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai Miyagi, JapanSearch for more papers by this authorTomohiko Fukuda, Tomohiko Fukuda Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai Miyagi, JapanSearch for more papers by this authorTomoya Isaji, Tomoya Isaji Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai Miyagi, JapanSearch for more papers by this authorHirokazu Hashimoto, Hirokazu Hashimoto Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai Miyagi, JapanSearch for more papers by this authorYuqin Wang, Yuqin Wang Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai Miyagi, JapanSearch for more papers by this authorJianguo Gu, Corresponding Author Jianguo Gu [email protected] Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai Miyagi, JapanCorrespondence: Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai Miyagi, 981-8558, Japan. E-mail: [email protected]Search for more papers by this author Wei Gu, Wei Gu Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai Miyagi, JapanSearch for more papers by this authorTomohiko Fukuda, Tomohiko Fukuda Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai Miyagi, JapanSearch for more papers by this authorTomoya Isaji, Tomoya Isaji Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai Miyagi, JapanSearch for more papers by this authorHirokazu Hashimoto, Hirokazu Hashimoto Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai Miyagi, JapanSearch for more papers by this authorYuqin Wang, Yuqin Wang Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai Miyagi, JapanSearch for more papers by this authorJianguo Gu, Corresponding Author Jianguo Gu [email protected] Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai Miyagi, JapanCorrespondence: Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai Miyagi, 981-8558, Japan. E-mail: [email protected]Search for more papers by this author First published: 24 June 2013 https://doi.org/10.1096/fj.12-225805Citations: 4Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract It is well known that α1,6-fucosyltransferase (Fut8) and its products, α1,6-fucosylated N-glycans, are highly expressed in brain tissue. Recently, we reported that Fut8-knockout mice exhibited multiple behavioral abnormalities with a schizophrenia-like phenotype, suggesting that α1,6-fucosylation plays important roles in the brain and neuron system. In the present study, we screened several neural cell lines and found that PC12 cells express the highest levels of α1,6-fucosylation. The knockdown (KD) of Fut8 promoted a significant enhancement of neurite formation and induction of neurofilament expression. Surprisingly, the levels of phospho-Smad2 were greatly increased in the KD cells. Finally, we found that the activin-mediated signal pathway was essential for these changes in KD cells. Exogenous activin, not TGF-β1, induced neurite outgrowth and phospho-Smad2. In addition, the α1,6-fucosylation level on the activin receptors was greatly decreased in KD cells, while the total expression level was unchanged, suggesting that α1,6-fucosylation negatively regulated activin-mediated signaling. Furthermore, inhibition of activin receptor-mediated signaling or restoration of Fut8 expression rescued cell morphology and phospho-Smad2 levels, which were enhanced in KD cells. Considering the fact that α1,6-fucosylation is important for TGF-β-mediated signaling, the results of this study strongly suggest that Fut8 plays a dual role in TGF-β/activin-mediated signaling.—Gu, W., Fukuda, T., Isaji, T., Hashimoto, H., Wang, Y., Gu, J., α1,6-Fucosylation regulates neurite formation via the activin/phospho-Smad2 pathway in PC12 cells: the implicated dual effects of Fut8 for TGF-β/activin-mediated signaling. FASEB J. 27, 3947–3958 (2013). www.fasebj.org Citing Literature Volume27, Issue10October 2013Pages 3947-3958 RelatedInformation