Membrane lipid rafts provide a specialized microenvironment enriched with sphingolipids and phospholipids containing saturated fatty acids and serve as a platform for various intracellular signalling pathways. PtdGlc (phosphatidylglucoside) is a type of glycophospholipid localized in the outer leaflet of the plasma membrane. Owing to PtdGlc's unique fatty acid composition, exclusively composed of C18:0 at sn-1 and C20:0 at sn-2 of the glycerol backbone, it tends to form PGLRs (PtdGlc-enriched lipid rafts). Previously, we demonstrated that PGLRs reside on the cell surface of astroglial cells from fetal rat brain [Nagatsuka, Horibata, Yamazaki, Kinoshita, Shinoda, Hashikawa, Koshino, Nakamura and Hirabayashi (2006) Biochemistry 45, 8742–8750]. In the present study, we observed PGLRs in astroglial lineage cells at mid-embryonic to early-postnatal stages of developing mouse cortex. This suggests that PGLRs are developmentally correlated with astroglial differentiation during fetal cortical development. Our cell culture studies with multipotent neural progenitor cells prepared from fetal mouse telencephalon demonstrated that treatment with EGF (epidermal growth factor) or anti-PtdGlc antibody caused recruitment of EGFRs (EGF receptors) into lipid raft compartments, leading to activation of EGFRs. Moreover, the activation of EGFRs by antibody triggered downstream tyrosine kinase signalling and induced marked GFAP (glial fibrillary acidic protein) expression via the JAK (Janus kinase)/STAT (signal transducer and activator of transcription) signalling pathway. These findings strongly suggest that PGLRs are physiologically coupled to activated EGFRs on neural progenitor cells during fetal cortical development, and thereby play a distinct role in mediating astrogliogenesis.
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Research Article|
April 14 2009
Lipid rafts enriched in phosphatidylglucoside direct astroglial differentiation by regulating tyrosine kinase activity of epidermal growth factor receptors
Masami O. Kinoshita;
Masami O. Kinoshita
*Hirabayashi Research Unit, RIKEN Brain Science Institute, Saitama 351-0198, Japan
†Department of Regulation Biology, Graduate School of Science and Engineering, Saitama University, Saitama 338-8570, Japan
††CREST, Japan Science Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan
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Shigeki Furuya;
Shigeki Furuya
‡Laboratory of Metabolic Regulation Research, Kyushu University Bio-Architecture Centre, Fukuoka 812-8581, Japan
††CREST, Japan Science Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan
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Shinya Ito;
Shinya Ito
§Hitachi High-Technologies Corp., Tokyo 105-8717, Japan
††CREST, Japan Science Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan
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Yoko Shinoda;
Yoko Shinoda
*Hirabayashi Research Unit, RIKEN Brain Science Institute, Saitama 351-0198, Japan
††CREST, Japan Science Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan
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Yasuhiro Yamazaki;
Yasuhiro Yamazaki
∥Department of Pharmaco-Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan
††CREST, Japan Science Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan
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Peter Greimel;
Peter Greimel
*Hirabayashi Research Unit, RIKEN Brain Science Institute, Saitama 351-0198, Japan
¶Advanced Science Institute, RIKEN, Saitama 351-0198, Japan
††CREST, Japan Science Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan
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Yukishige Ito;
Yukishige Ito
¶Advanced Science Institute, RIKEN, Saitama 351-0198, Japan
††CREST, Japan Science Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan
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Tsutomu Hashikawa;
Tsutomu Hashikawa
**Supporting Unit for Neuromorphological Analysis, RIKEN Brain Science Institute, Saitama 351-0198, Japan
††CREST, Japan Science Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan
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Takeo Machida;
Takeo Machida
†Department of Regulation Biology, Graduate School of Science and Engineering, Saitama University, Saitama 338-8570, Japan
††CREST, Japan Science Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan
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Yasuko Nagatsuka;
Yasuko Nagatsuka
*Hirabayashi Research Unit, RIKEN Brain Science Institute, Saitama 351-0198, Japan
††CREST, Japan Science Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan
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Yoshio Hirabayashi
Yoshio Hirabayashi
1
*Hirabayashi Research Unit, RIKEN Brain Science Institute, Saitama 351-0198, Japan
†Department of Regulation Biology, Graduate School of Science and Engineering, Saitama University, Saitama 338-8570, Japan
††CREST, Japan Science Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan
1To whom correspondence should be addressed (email hirabaya@riken.jp).
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Publisher: Portland Press Ltd
Received:
September 18 2008
Revision Received:
January 09 2009
Accepted:
January 27 2009
Accepted Manuscript online:
January 27 2009
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2009 Biochemical Society
2009
Biochem J (2009) 419 (3): 565–575.
Article history
Received:
September 18 2008
Revision Received:
January 09 2009
Accepted:
January 27 2009
Accepted Manuscript online:
January 27 2009
Citation
Masami O. Kinoshita, Shigeki Furuya, Shinya Ito, Yoko Shinoda, Yasuhiro Yamazaki, Peter Greimel, Yukishige Ito, Tsutomu Hashikawa, Takeo Machida, Yasuko Nagatsuka, Yoshio Hirabayashi; Lipid rafts enriched in phosphatidylglucoside direct astroglial differentiation by regulating tyrosine kinase activity of epidermal growth factor receptors. Biochem J 1 May 2009; 419 (3): 565–575. doi: https://doi.org/10.1042/BJ20081896
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