Neurodevelopment is orchestrated by a series of growth factor–HS (heparan sulfate) interactions which are involved in neuritogenesis. GLCE (glucuronic acid epimerase) is a critical enzyme involved in HS synthesis, which converts GlcA (D-glucuronic acid) into IdoA (L-iduronic acid). However, the function of GLCE in neuritogenesis is largely unknown. In the present study we showed that GLCE depletion caused arrested PC12 cell growth and promoted the cell neuritogenesis and differentiation induced by NGF (nerve growth factor). PC12 cell growth was boosted by overexpression of GLCE, and neuritogenesis was impaired when GLCE depletion was rescued. Interestingly, overexpression of wild-type GLCE with Y168A and Y222A mutations led to enhanced PC12 cell growth and attenuated the neuritogenesis triggered by GLCE silencing. We showed further that GLCE depletion blocked SMAD1/5/8 phosphorylation; however, this signalling could be restored by GLCE or the mutation of its active enzymatic site. In addition, the downstream effector of SMAD1/5/8, ID3 (inhibitor of DNA binding/differentiation 3) was induced by GLCE. ID3 silencing inhibited PC12 cell growth and induced cell neuritogenesis and differentiation. In addition, ectopic expression of ID3 partially rescued the phenotype caused by GLCE silencing. The results of the present study suggest that GLCE plays a key role in PC12 cell growth and neuritogenesis through SMAD/ID3 signalling.
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Research Article|
March 28 2014
GLCE regulates PC12 cell neuritogenesis induced by nerve growth factor through activating SMAD/ID3 signalling Available to Purchase
Jie Li;
Jie Li
*School of Life Sciences, Northeast Normal University, Changchun 130024, China
†Glycochemistry & Glycobiology Lab, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
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Jianping Fang;
Jianping Fang
†Glycochemistry & Glycobiology Lab, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
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Yi Qin;
Yi Qin
†Glycochemistry & Glycobiology Lab, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
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Wenfeng Liao;
Wenfeng Liao
†Glycochemistry & Glycobiology Lab, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
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Hailing Liu;
Hailing Liu
†Glycochemistry & Glycobiology Lab, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
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Yifa Zhou;
Yifa Zhou
1
*School of Life Sciences, Northeast Normal University, Changchun 130024, China
1Correspondence may be addressed to either of these authors ([email protected] or [email protected]).
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Kan Ding
Kan Ding
1
†Glycochemistry & Glycobiology Lab, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
1Correspondence may be addressed to either of these authors ([email protected] or [email protected]).
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Publisher: Portland Press Ltd
Received:
October 11 2013
Revision Received:
January 21 2014
Accepted:
February 05 2014
Accepted Manuscript online:
February 05 2014
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem J (2014) 459 (2): 405–415.
Article history
Received:
October 11 2013
Revision Received:
January 21 2014
Accepted:
February 05 2014
Accepted Manuscript online:
February 05 2014
Citation
Jie Li, Jianping Fang, Yi Qin, Wenfeng Liao, Hailing Liu, Yifa Zhou, Kan Ding; GLCE regulates PC12 cell neuritogenesis induced by nerve growth factor through activating SMAD/ID3 signalling. Biochem J 15 April 2014; 459 (2): 405–415. doi: https://doi.org/10.1042/BJ20131360
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