In order to search for novel components of lipid membrane microdomains involved in neural signalling pathways, mAbs (monoclonal antibodies) were raised against the detergent-insoluble membrane fraction of PC12 (pheochromocytoma) cells. Among the 22 hybrid clones, mAb PR#1 specifically detected a fucoganglioside Fuc(Gal)-GM1 [α-fucosyl(α-galactosyl)-GM1], a ganglioside homologous with GM1a (II3NeuAc,GgOse4Cer), as a novel member of microdomain components with biological functions. In the presence of mAb PR#1 in the culture medium, the outgrowth of neurites was induced in PC12 cells in a dose-dependent manner, with no effects on cell proliferation, suggesting that Fuc(Gal)-GM1 is preferentially involved in PC12 cell neuritogenesis. Effects through Fuc(Gal)-GM1 were different from those through GM1a during differentiation, e.g. under PR#1 treatment on Fuc(Gal)-GM1, round cell bodies with thinner cell processes were induced, whereas treatment with CTB (cholera toxin B subunit), a specific probe for GM1a, produced flattened cell bodies with thicker pro-cesses. Molecular analysis demonstrated that the PR#1–Fuc(Gal)-GM1 pathway was associated with Fyn and Yes of the Src family of kinases, although Src itself was not involved. No association was found with TrkA (tropomyosin receptor kinase A) and ERKs (extracellular-signal-regulated kinases), which are responsible for GM1a-induced differentiation. From these findings, it is suggested that a fucoganglioside Fuc(Gal)-GM1 provides a functional platform distinct from that of GM1a for signal transduction in PC12 cell differentiation.
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Research Article|
September 12 2007
Fucoganglioside α-fucosyl(α-galactosyl)-GM1: a novel member of lipid membrane microdomain components involved in PC12 cell neuritogenesis
Yasuhiro Yamazaki;
Yasuhiro Yamazaki
*Laboratory for Neural Architecture, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan
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Yasuhiro Horibata;
Yasuhiro Horibata
†Hirabayashi Research Unit, Neural Circuit Research Group, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan
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Yasuko Nagatsuka;
Yasuko Nagatsuka
†Hirabayashi Research Unit, Neural Circuit Research Group, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan
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Yoshio Hirabayashi;
Yoshio Hirabayashi
†Hirabayashi Research Unit, Neural Circuit Research Group, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan
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Tsutomu Hashikawa
Tsutomu Hashikawa
1
*Laboratory for Neural Architecture, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan
1To whom correspondence should be addressed (email tom@brain.riken.jp).
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Publisher: Portland Press Ltd
Received:
January 16 2007
Revision Received:
June 04 2007
Accepted:
July 04 2007
Accepted Manuscript online:
July 04 2007
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2007 Biochemical Society
2007
Biochem J (2007) 407 (1): 31–40.
Article history
Received:
January 16 2007
Revision Received:
June 04 2007
Accepted:
July 04 2007
Accepted Manuscript online:
July 04 2007
Citation
Yasuhiro Yamazaki, Yasuhiro Horibata, Yasuko Nagatsuka, Yoshio Hirabayashi, Tsutomu Hashikawa; Fucoganglioside α-fucosyl(α-galactosyl)-GM1: a novel member of lipid membrane microdomain components involved in PC12 cell neuritogenesis. Biochem J 1 October 2007; 407 (1): 31–40. doi: https://doi.org/10.1042/BJ20070090
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