2004 Fiscal Year Final Research Report Summary
Analysis of Signal Transduction Machineries Involving Two Types of NELL Proteins in the Differentiation Process of Neural Crest-derived Cells
| Project/Area Number |
15300126
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Osaka University |
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Principal Investigator |
KURODA Shun'ichi Osaka University, The Institute of Scientific and Industrial Research, Associate Professor, 産業科学研究所, 助教授 (60263406)
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| Project Period (FY) |
2003 – 2004
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| Keywords | neuron / osteoblast / growth factor / neuralcrest cells / EGF-like domain |
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| Research Abstract |
NELL proteins (NELL1,NELL2), found in 1999 by us, possess a unique molecular organization. From N- to C-terminal, a signal peptide, thrombospondin 1-N terminal domain, EGF-like motifs, and vWF-derived motifs are found in both proteins. These Two 140-kDa proteins show about 55% similarity in the amino acid sequence level, are synthesized as a secreted protein, and form a about 400-kDa homotrimeric proteins. By our previous studies, since NELL1 mRNA was significantly expressed at the suture of craniocynostosis patients' skull, the NELL1 was finally demonstrated as a novel bone morphogenic protein(BMP). Unlike the conventional BMPs (e.x., BMP2,BMP4,BMP7), the NELL1 protein showed exclusively the induction of bone formation in osteoblast cells and not affected the determination of dorsal-ventral axes in the embryos.
In this study, we established the continuous synthesis of NELL proteins using insect cell system (continuous, stable, and serum-free) and succeeded in the preparation of large amount of pure NELL proteins. These NELL proteins facilitated us to identify the novel molecules as candidates of NELL-specific receptors by using expression cloning techniques and analyze the 3D-structure by using an X-ray crystallographic technique. Furthermore, we succeeded in the establishing NELL1-overexpressing transgenic mice and NELL2-deflcieat mice for analyzing the physiological roles of NELL proteins.
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Research Products
(8 results)
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[Journal Article] Spatial Learning of Mice Lacking a Neuron-Specific EGF Family Protein, NELL2.2005
Author(s)
Matsuyama, S., Doe, N., Kunihara, N., Tanizawa, K., Kuroda, S., Iso, H., Horie, M.
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Journal Title
J.Pharmacol.Sci. (in press)
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Enhanced Long-term Potentiation In Vivo in the Dentate Gyrus of Mice Lacking a Neuron-specific EGF Family Protein, NELL2.2004
Author(s)
Matsuyama, S., Aiharam K., Nishino, N., Takeda, S., Tanizawa, K., Kuroda, S., Horie, M.
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Journal Title
Neuroreport 15
Pages: 417-420
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Overexpression of Nell-1, a Craniosynostosis Associated Gene, Induces Apoptosis in Osteoblasts during Craniofacial Development.2003
Author(s)
Zhang, X., Carpenter, D., Bokui, N., Soo, C., Miao, S., Truong, T., Wu, B., Chen, I., Vastardis, H., Tanizawa, K., Kuroda, S., Ting, K.
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Journal Title
J.Bone Mineral Res. 18
Pages: 2126-2134
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A Neuron-specific EGF Family Protein, NELL2, Promotes Survival of Neurons through Mitogen-activated Protein Kinases.2003
Author(s)
Aihara, K., Kuroda, S., Kanayama, N., Matsuyama, S., Tanizawa, K., Horie, K.
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Journal Title
Brain Res.Mol.Brain Res. 116
Pages: 86-93
Description
「研究成果報告書概要(欧文)」より
